2,365 research outputs found
Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium
Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating
communities persist despite competition among community members. Theory suggests that non-random spatial structures
contribute to the persistence of mixed communities; when particular structures form, they may provide associated
community members with a growth advantage over unassociated members. If true, this has implications for the rise and
persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances
of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a
synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a
biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable
growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes
in the initial environment; in other words, the structure enhances the ability of the consortium to survive
environmental disruptions. Second, when the layered structure forms in downstream environments the consortium
accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the
global productivity of the consortium. We also observed that the layered structure only assembles in downstream
environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for
self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques
of synthetic biology in elucidating fundamental biological principles
E7(7) invariant Lagrangian of d=4 N=8 supergravity
We present an E7(7) invariant Lagrangian that leads to the equations of
motion of d=4 N=8 supergravity without using Lagrange multipliers. The
superinvariance of this new action and the closure of the supersymmetry algebra
are proved explicitly for the terms that differ from the Cremmer--Julia
formulation. Since the diffeomorphism symmetry is not realized in the standard
way on the vector fields, we switch to the Hamiltonian formulation in order to
prove the invariance of the E7(7) invariant action under general coordinate
transformations. We also construct the conserved E7(7)-Noether current of
maximal supergravity and we conclude with comments on the implications of this
manifest off-shell E7(7)-symmetry for quantizing d=4 N=8 supergravity, in
particular on the E7(7)-action on phase space.Comment: 45 pages, references adde
Improving the use of research evidence in guideline development: 9. Grading evidence and recommendations
BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the ninth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on grading evidence and recommendations in guidelines. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a full systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: Should WHO grade the quality of evidence and the strength of recommendations? • Users of recommendations need to know how much confidence they can place in the underlying evidence and the recommendations. The degree of confidence depends on a number of factors and requires complex judgments. These judgments should be made explicitly in WHO recommendations. A systematic and explicit approach to making judgments about the quality of evidence and the strength of recommendations can help to prevent errors, facilitate critical appraisal of these judgments, and can help to improve communication of this information. What criteria should be used to grade evidence and recommendations? • Both the quality of evidence and the strength of recommendations should be graded. The criteria used to grade the strength of recommendations should include the quality of the underlying evidence, but should not be limited to that. • The approach to grading should be one that has wide international support and is suitable for a wide range of different types of recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which is currently suggested in the Guidelines for WHO Guidelines, is being used by an increasing number of other organizations internationally. It should be used more consistently by WHO. Further developments of this approach should ensure its wide applicability. Should WHO use the same grading system for all of its recommendations? • Although there are arguments for and against using the same grading system across a wide range of different types of recommendations, WHO should use a uniform grading system to prevent confusion for developers and users of recommendations
Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight
We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel
Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands
"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)
Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions
The first-principles periodic linear combination of atomic orbitals method
within the framework of density functional theory implemented in the CRYSTAL06
code has been applied to explore effect of pressure on the Compton profiles and
autocorrelation functions of MgO. Calculations are performed for the B1, B2,
B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk
moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to
B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42
and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2
are found to occur at 340 and 410 GPa respectively. The pressure dependent
changes are observed largely in the valence electrons Compton profiles whereas
core profiles are almost independent of the pressure in all MgO polymorphs.
Increase in pressure results in broadening of the valence Compton profiles. The
principal maxima in the second derivative of Compton profiles shifts towards
high momentum side in all structures. Reorganization of momentum density in the
B1 to B2 structural phase transition is seen in the first and second
derivatives before and after the transition pressure. Features of the
autocorrelation functions shift towards lower r side with increment in
pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials
Scienc
A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone
Recommended standardized procedures for determining exhaled lower respiratory
nitric oxide and nasal nitric oxide have been developed by task forces of the
European Respiratory Society and the American Thoracic Society. These
recommendations have paved the way for the measurement of nitric oxide to
become a diagnostic tool for specific clinical applications. It would be
desirable to develop similar guidelines for the sampling of other trace gases
in exhaled breath, especially volatile organic compounds (VOCs) which reflect
ongoing metabolism. The concentrations of water-soluble, blood-borne substances
in exhaled breath are influenced by: (i) breathing patterns affecting gas
exchange in the conducting airways; (ii) the concentrations in the
tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations
of the compound. The classical Farhi equation takes only the alveolar
concentrations into account. Real-time measurements of acetone in end-tidal
breath under an ergometer challenge show characteristics which cannot be
explained within the Farhi setting. Here we develop a compartment model that
reliably captures these profiles and is capable of relating breath to the
systemic concentrations of acetone. By comparison with experimental data it is
inferred that the major part of variability in breath acetone concentrations
(e.g., in response to moderate exercise or altered breathing patterns) can be
attributed to airway gas exchange, with minimal changes of the underlying blood
and tissue concentrations. Moreover, it is deduced that measured end-tidal
breath concentrations of acetone determined during resting conditions and free
breathing will be rather poor indicators for endogenous levels. Particularly,
the current formulation includes the classical Farhi and the Scheid series
inhomogeneity model as special limiting cases.Comment: 38 page
LRRK2 deficiency induced mitochondrial Ca2+ efflux inhibition can be rescued by Na+/Ca2+/Li+ exchanger upregulation
Variants of leucine-rich repeat kinase 2 (lrrk2) are associated with an increased risk in developing Parkinson’s disease (PD). Mitochondrial dysfunction and specifically mitochondrial Ca2+ handling has been linked to the pathogenesis of PD. Here we describe for the second time a mitochondrial Ca2+ efflux deficiency in a model displaying alterations in a PD-associated risk protein. LRRK2 deletion, inhibition and mutations led to an impaired mitochondrial Ca2+ extrusion via Na+/Ca2+/Li+ exchanger (NCLX) which in turn lowered mitochondrial permeability transition pore (PTP) opening threshold and increased cell death. The mitochondrial membrane potential was found not to be the underlying cause for the Ca2+ extrusion deficiency. NCLX activity was rescued by a direct (phosphomimetic NCLX mutant) and indirect (protein kinase A) activation which in turn elevated the PTP opening threshold. Therefore, at least two PD-associated risk protein pathways appear to converge on NCLX controlling mitochondrial Ca2+ extrusion and therefore mitochondrial health. Since mitochondrial Ca2+ overload has been described in many neurological disorders this study warrants further studies into NCLX as a potential therapeutic target
Attentional bias retraining in cigarette smokers attempting smoking cessation (ARTS): study protocol for a double bline randomised controlled trial
YesSmokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is
known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking.
Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although
these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple
sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation.
This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop
smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training.
Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal
nicotine patches for 8–12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures
are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks
post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at
4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months
and 6 months post-quit.
This is the first randomised controlled trial of attentional retraining in smokers attempting cessation.
This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction.National Institute for Health Research (NIHR) Doctoral Research Fellowship (DRF) awarded to RB (DRF-2009-02-15
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