1,610 research outputs found
Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: results of the COSMOS mixed-methods study
Background: Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS). Objective: To determine the variables that affect continuation or discontinuation of the use of CIC. Methods: A three-part mixed-method study (prospective longitudinal cohort (n = 56), longitudinal qualitative interviews (n = 20) and retrospective survey (n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual’s age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity. Results: For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation. Conclusion: Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person’s readiness to try CIC
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The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice.
During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic
GeneMill: A 21st century platform for innovation
GeneMill officially launched on 4th February 2016 and is an open access academic facility located at The University of Liverpool that has been established for the high-throughput construction and testing of synthetic DNA constructs. GeneMill provides end-to-end design, construction and phenotypic characterization of small to large gene constructs or genetic circuits/pathways for academic and industrial applications. Thus, GeneMill is equipping the scientific community with easy access to the validated tools required to explore the possibilities of Synthetic Biology
Testing for Network and Spatial Autocorrelation
Testing for dependence has been a well-established component of spatial
statistical analyses for decades. In particular, several popular test
statistics have desirable properties for testing for the presence of spatial
autocorrelation in continuous variables. In this paper we propose two
contributions to the literature on tests for autocorrelation. First, we propose
a new test for autocorrelation in categorical variables. While some methods
currently exist for assessing spatial autocorrelation in categorical variables,
the most popular method is unwieldy, somewhat ad hoc, and fails to provide
grounds for a single omnibus test. Second, we discuss the importance of testing
for autocorrelation in data sampled from the nodes of a network, motivated by
social network applications. We demonstrate that our proposed statistic for
categorical variables can both be used in the spatial and network setting
Quantum resource estimates for computing elliptic curve discrete logarithms
We give precise quantum resource estimates for Shor's algorithm to compute
discrete logarithms on elliptic curves over prime fields. The estimates are
derived from a simulation of a Toffoli gate network for controlled elliptic
curve point addition, implemented within the framework of the quantum computing
software tool suite LIQ. We determine circuit implementations for
reversible modular arithmetic, including modular addition, multiplication and
inversion, as well as reversible elliptic curve point addition. We conclude
that elliptic curve discrete logarithms on an elliptic curve defined over an
-bit prime field can be computed on a quantum computer with at most qubits using a quantum circuit of at most Toffoli gates. We are able to classically simulate the
Toffoli networks corresponding to the controlled elliptic curve point addition
as the core piece of Shor's algorithm for the NIST standard curves P-192,
P-224, P-256, P-384 and P-521. Our approach allows gate-level comparisons to
recent resource estimates for Shor's factoring algorithm. The results also
support estimates given earlier by Proos and Zalka and indicate that, for
current parameters at comparable classical security levels, the number of
qubits required to tackle elliptic curves is less than for attacking RSA,
suggesting that indeed ECC is an easier target than RSA.Comment: 24 pages, 2 tables, 11 figures. v2: typos fixed and reference added.
ASIACRYPT 201
Explosive Nucleosynthesis: What we learned and what we still do not understand
This review touches on historical aspects, going back to the early days of
nuclear astrophysics, initiated by BFH and Cameron, discusses (i) the
required nuclear input from reaction rates and decay properties up to the
nuclear equation of state, continues (ii) with the tools to perform
nucleosynthesis calculations and (iii) early parametrized nucleosynthesis
studies, before (iv) reliable stellar models became available for the late
stages of stellar evolution. It passes then through (v) explosive environments
from core-collapse supernovae to explosive events in binary systems (including
type Ia supernovae and compact binary mergers), and finally (vi) discusses the
role of all these nucleosynthesis production sites in the evolution of
galaxies. The focus is put on the comparison of early ideas and present, very
recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of
Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018
Silicon Atomic Quantum Dots Enable Beyond-CMOS Electronics
We review our recent efforts in building atom-scale quantum-dot cellular
automata circuits on a silicon surface. Our building block consists of silicon
dangling bond on a H-Si(001) surface, which has been shown to act as a quantum
dot. First the fabrication, experimental imaging, and charging character of the
dangling bond are discussed. We then show how precise assemblies of such dots
can be created to form artificial molecules. Such complex structures can be
used as systems with custom optical properties, circuit elements for
quantum-dot cellular automata, and quantum computing. Considerations on
macro-to-atom connections are discussed.Comment: 28 pages, 19 figure
CMB Telescopes and Optical Systems
The cosmic microwave background radiation (CMB) is now firmly established as
a fundamental and essential probe of the geometry, constituents, and birth of
the Universe. The CMB is a potent observable because it can be measured with
precision and accuracy. Just as importantly, theoretical models of the Universe
can predict the characteristics of the CMB to high accuracy, and those
predictions can be directly compared to observations. There are multiple
aspects associated with making a precise measurement. In this review, we focus
on optical components for the instrumentation used to measure the CMB
polarization and temperature anisotropy. We begin with an overview of general
considerations for CMB observations and discuss common concepts used in the
community. We next consider a variety of alternatives available for a designer
of a CMB telescope. Our discussion is guided by the ground and balloon-based
instruments that have been implemented over the years. In the same vein, we
compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the
South Pole Telescope (SPT). CMB interferometers are presented briefly. We
conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and
Planck, to demonstrate a remarkable evolution in design, sensitivity,
resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1:
Telescopes and Instrumentatio
Prediction of peptide and protein propensity for amyloid formation
Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation
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