Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Supermembrane interaction with dynamical D=4 N=1 supergravity. Superfield Lagrangian description and spacetime equations of motion

We obtain the complete set of equations of motion for the interacting system of supermembrane and dynamical D=4 N = 1 supergravity by varying its complete superfield action and writing the resulting superfield equations in the special gauge where the supermembrane Goldstone field is set to zero. We solve the equations for auxiliary fields and discuss the effect of dynamical generation of cosmological constant in the Einstein equation of interacting system and its renormalization due to some regular contributions from supermembrane. These two effects (discussed in late 70th and 80th, in the bosonic perspective and in the supergravity literature) result in that, generically, the cosmological constant has different values in the branches of the spacetime separated by the supermembrane worldvolume.Comment: 23 pages, no figures. V2 two references added, 24 page

Time-calibrated molecular phylogeny of pteropods

© 2017 Burridge et al. This is an open access article distributed under the terms of the [4.0] Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor

Blood Substitutes in Cardiac Surgery

A safe, inexpensive, noninfectious substitute for red blood cells has long been sought. Despite tremendous advances in blood banking, the logistics of collecting, transporting, and storing human red blood cells contin ues to create infection and shortage problems. The two basic types of blood substitutes currently under devel opment are hemoglobin based and fluorocarbon based. Although they each transport oxygen differently, the basic advantages and limitations are the same. Blood substitute advantages include the unique capacity for room temperature storage, noninfectivity, adequate supply, and low toxicity. Restrictions include limited dosing in the acute period, limited intravascular half-life and, for the fluorocarbons, a requirement for a high PaO2. In addition, there remain questions about the relationship of nitric oxide metabolism to hypertension in hemoglobin solutions. Early clinical and laboratory trials have shown that both types of solutions are effective oxygen-delivery agents, with acceptable side- effect profiles. Clinical trials are currently underway to determine the safety and efficacy of these solutions in patients undergoing cardiopulmonary bypass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68576/2/10.1177_108925329800200403.pd

Robust Poisson Surface Reconstruction

Abstract. We propose a method to reconstruct surfaces from oriented point clouds with non-uniform sampling and noise by formulating the problem as a convex minimization that reconstructs the indicator func-tion of the surface’s interior. Compared to previous models, our recon-struction is robust to noise and outliers because it substitutes the least-squares fidelity term by a robust Huber penalty; this allows to recover sharp corners and avoids the shrinking bias of least squares. We choose an implicit parametrization to reconstruct surfaces of unknown topology and close large gaps in the point cloud. For an efficient representation, we approximate the implicit function by a hierarchy of locally supported basis elements adapted to the geometry of the surface. Unlike ad-hoc bases over an octree, our hierarchical B-splines from isogeometric analysis locally adapt the mesh and degree of the splines during reconstruction. The hi-erarchical structure of the basis speeds-up the minimization and efficiently represents clustered data. We also advocate for convex optimization, in-stead isogeometric finite-element techniques, to efficiently solve the min-imization and allow for non-differentiable functionals. Experiments show state-of-the-art performance within a more flexible framework.

Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors

© 2020, The Author(s). We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other rodent disease models

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Plasmonically Enhanced Reflectance of Heat Radiation from Low-Bandgap Semiconductor Microinclusions

Increased reflectance from the inclusion of highly scattering particles at low volume fractions in an insulating dielectric offers a promising way to reduce radiative thermal losses at high temperatures. Here, we investigate plasmonic resonance driven enhanced scattering from microinclusions of low-bandgap semiconductors (InP, Si, Ge, PbS, InAs and Te) in an insulating composite to tailor its infrared reflectance for minimizing thermal losses from radiative transfer. To this end, we compute the spectral properties of the microcomposites using Monte Carlo modeling and compare them with results from Fresnel equations. The role of particle size-dependent Mie scattering and absorption efficiencies, and, scattering anisotropy are studied to identify the optimal microinclusion size and material parameters for maximizing the reflectance of the thermal radiation. For composites with Si and Ge microinclusions we obtain reflectance efficiencies of 57 - 65% for the incident blackbody radiation from sources at temperatures in the range 400 - 1600 {\deg}C. Furthermore, we observe a broadbanding of the reflectance spectra from the plasmonic resonances due to charge carriers generated from defect states within the semiconductor bandgap. Our results thus open up the possibility of developing efficient high-temperature thermal insulators through use of the low-bandgap semiconductor microinclusions in insulating dielectrics.Comment: Main article (8 Figures and 2 Tables) + Supporting Information (8 Figures