62 resultados para Signatures of Selection


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Extreme arid regions in the worlds' major deserts are typified by quartz pavement terrain. Cryptic hypolithic communities colonize the ventral surface of quartz rocks and this habitat is characterized by a relative lack of environmental and trophic complexity. Combined with readily identifiable major environmental stressors this provides a tractable model system for determining the relative role of stochastic and deterministic drivers in community assembly. Through analyzing an original, worldwide data set of 16S rRNA-gene defined bacterial communities from the most extreme deserts on the Earth, we show that functional assemblages within the communities were subject to different assembly influences. Null models applied to the photosynthetic assemblage revealed that stochastic processes exerted most effect on the assemblage, although the level of community dissimilarity varied between continents in a manner not always consistent with neutral models. The heterotrophic assemblages displayed signatures of niche processes across four continents, whereas in other cases they conformed to neutral predictions. Importantly, for continents where neutrality was either rejected or accepted, assembly drivers differed between the two functional groups. This study demonstrates that multi-trophic microbial systems may not be fully described by a single set of niche or neutral assembly rules and that stochasticity is likely a major determinant of such systems, with significant variation in the influence of these determinants on a global scale.

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PurposeThe World Health Organisation (WHO) identified patient safety in surgery as an important public health matter and advised the adoption of a universal peri-operative surgical checklist. An adapted version of the WHO checklist has been mandatory in the National Health Service since 2010. Wrong intraocular lens (IOL) implantation is a particular safety concern in ophthalmology. The Royal College of Ophthalmologists launched a bespoke checklist for cataract surgery in 2010 to reduce the likelihood of preventable errors. We sought to ascertain the use of checklists in cataract surgery in 2012.Patients and methodsA survey of members of the Royal College of Ophthalmologists seeking views on the use of checklists in cataract surgery. Four hundred and sixty-nine completed responses were received (18% response rate).ResultsRespondents worked in England (75%), Scotland (11%), Wales (5%), Northern Ireland (2%), the Republic of Ireland (1%), and overseas (6%). Ninety-four per cent of respondents support the use of a checklist for cataract surgery and 85% say that they always use a checklist before cataract surgery. Sixty-seven per cent of cataract surgeons stated they undertake a pre-operative team brief. Thirty-six per cent use a cataract surgery checklist developed locally, 18% use the college's bespoke cataract surgery checklist, 39% use a generic surgical checklist, and 4% reported that they do not use a checklist.ConclusionNinety-three per cent of cataract surgeons responding to the questionnaire report using a surgical checklist and 67% use a team brief. However, only 54% use a checklist, which addresses the selection of the correct intraocular implant. We recommend wider adoption of checklists, which address risks relevant to cataract surgery, in particular the possibility of selection of an incorrect IOL.Eye advance online publication, 24 May 2013; doi:10.1038/eye.2013.101.

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The self-consistent interaction between energetic particles and self-generated hydromagnetic waves in a cosmic ray pressure dominated plasma is considered. Using a three-dimensional hybrid magnetohydrodynamics (MHD)-kinetic code, which utilizes a spherical harmonic expansion of the Vlasov-Fokker-Planck equation, high-resolution simulations of the magnetic field growth including feedback on the cosmic rays are carried out. It is found that for shocks with high cosmic ray acceleration efficiency, the magnetic fields become highly disorganized, resulting in near isotropic diffusion, independent of the initial orientation of the ambient magnetic field. The possibility of sub-Bohm diffusion is demonstrated for parallel shocks, while the diffusion coefficient approaches the Bohm limit from below for oblique shocks. This universal behaviour suggests that Bohm diffusion in the root-mean-squared field inferred from observation may provide a realistic estimate for the maximum energy acceleration time-scale in young supernova remnants. Although disordered, the magnetic field is not self-similar suggesting a non-uniform energy-dependent behaviour of the energetic particle transport in the precursor. Possible indirect radiative signatures of cosmic ray driven magnetic field amplification are discussed.

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Analysis of molecular interaction and conformational dynamics of biomolecules is of paramount importance in understanding of their vital functions in complex biological systems, disease detection, and new drug development. Plasmonic biosensors based upon surface plasmon resonance and localized surface plasmon resonance have become the predominant workhorse for detecting accumulated biomass caused by molecular binding events. However, unlike surface-enhanced Raman spectroscopy (SERS), the plasmonic biosensors indeed are not suitable tools to interrogate vibrational signatures of conformational transitions required for biomolecules to interact. Here, we show that plasmonic metamaterials can offer two transducing channels for parallel acquisition of optical transmission and sensitive SERS spectra at the biointerface, simultaneously probing the conformational states and binding affinity of biomolecules, e.g. G-quadruplexes, in different environments (Fig. 1). We further demonstrate the use of the metamaterials for fingerprinting and detection of arginine-glycine-glycine domain of nucleolin, a cancer biomarker which specifically binds to a G-quadruplex, with the picomolar sensitivity. The dual-mode nanosensor will significantly contribute to unraveling the complexes of the conformational dynamics of biomolecules as well as to improving specificity of biodetection assays.

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Human listeners seem to have an impressive ability to recognize a wide variety of natural sounds. However, there is surprisingly little quantitative evidence to characterize this fundamental ability. Here the speed and accuracy of musical-sound recognition were measured psychophysically with a rich but acoustically balanced stimulus set. The set comprised recordings of notes from musical instruments and sung vowels. In a first experiment, reaction times were collected for three target categories: voice, percussion, and strings. In a go/no-go task, listeners reacted as quickly as possible to members of a target category while withholding responses to distractors (a diverse set of musical instruments). Results showed near-perfect accuracy and fast reaction times, particularly for voices. In a second experiment, voices were recognized among strings and vice-versa. Again, reaction times to voices were faster. In a third experiment, auditory chimeras were created to retain only spectral or temporal features of the voice. Chimeras were recognized accurately, but not as quickly as natural voices. Altogether, the data suggest rapid and accurate neural mechanisms for musical-sound recognition based on selectivity to complex spectro-temporal signatures of sound sources.

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Recent experiments on Au break junctions [Phys. Rev. Lett. 88 (2002) 216803] have characterized the nonlinear conductance of stretched short Au nanowires. They reveal in the voltage range 10-20 meV the signatures of dissipation effects, likely due to phonons in the nanowire, reducing the conductance below the quantized value of 2e(2)/h. We present here a theory, based on a model tight-binding Hamiltonian and on non-equilibrium Green's function techniques, which accounts for the main features of the experiment. The theory helps in revealing details of the experiment which need to be addressed with a more realistic, less idealized, theoretical framework. (C) 2004 Elsevier B.V. All rights reserved.

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The role of bacteria and viruses as aetiological agents in the pathogenesis of cancer has been well established for several sites, including a number of haematological malignancies. Less clear is the impact of such exposures on the subsequent development of multiple myeloma (MM). Using the population-based U.S. Surveillance Epidemiology and End Results-Medicare dataset, 15,318 elderly MM and 200,000 controls were identified to investigate the impact of 14 common community-acquired infections and risk of MM. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were adjusted for sex, age and calendar year of selection. The 13-month period prior to diagnosis/selection was excluded. Risk of MM was increased by 5-39% following Medicare claims for eight of the investigated infections. Positive associations were observed for several infections including bronchitis (adjusted OR 1.14, 95% CI 1.09-1.18), sinusitis (OR 1.15, 95% CI 1.10-1.20) pneumonia (OR 1.27, 95% CI 1.21-1.33), herpes zoster (OR 1.39, 95% CI 1.29-1.49) and cystitis (OR 1.09, 95% CI 1.05-1.14). Each of these infections remained significantly elevated following the exclusion of more than 6 years of claims data. Exposure to infectious antigens may therefore play a role in the development of MM. Alternatively, the observed associations may be a manifestation of an underlying immune disturbance present several years prior to MM diagnosis and thereby part of the natural history of disease progression.

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Since a key requirement of known life forms is available water (water activity; aw), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earth's present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth.

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Background: Selection bias in HIV prevalence estimates occurs if non-participation in testing is correlated with HIV status. Longitudinal data suggests that individuals who know or suspect they are HIV positive are less likely to participate in testing in HIV surveys, in which case methods to correct for missing data which are based on imputation and observed characteristics will produce biased results. Methods: The identity of the HIV survey interviewer is typically associated with HIV testing participation, but is unlikely to be correlated with HIV status. Interviewer identity can thus be used as a selection variable allowing estimation of Heckman-type selection models. These models produce asymptotically unbiased HIV prevalence estimates, even when non-participation is correlated with unobserved characteristics, such as knowledge of HIV status. We introduce a new random effects method to these selection models which overcomes non-convergence caused by collinearity, small sample bias, and incorrect inference in existing approaches. Our method is easy to implement in standard statistical software, and allows the construction of bootstrapped standard errors which adjust for the fact that the relationship between testing and HIV status is uncertain and needs to be estimated. Results: Using nationally representative data from the Demographic and Health Surveys, we illustrate our approach with new point estimates and confidence intervals (CI) for HIV prevalence among men in Ghana (2003) and Zambia (2007). In Ghana, we find little evidence of selection bias as our selection model gives an HIV prevalence estimate of 1.4% (95% CI 1.2% – 1.6%), compared to 1.6% among those with a valid HIV test. In Zambia, our selection model gives an HIV prevalence estimate of 16.3% (95% CI 11.0% - 18.4%), compared to 12.1% among those with a valid HIV test. Therefore, those who decline to test in Zambia are found to be more likely to be HIV positive. Conclusions: Our approach corrects for selection bias in HIV prevalence estimates, is possible to implement even when HIV prevalence or non-participation is very high or very low, and provides a practical solution to account for both sampling and parameter uncertainty in the estimation of confidence intervals. The wide confidence intervals estimated in an example with high HIV prevalence indicate that it is difficult to correct statistically for the bias that may occur when a large proportion of people refuse to test.

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Background The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision. We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. Objectives To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. Search methods We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. Selection criteria Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. Data collection and analysis Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. Main results Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). Authors' conclusions This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

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This paper investigates the potential improvement in signal reliability for outdoor short-range off-body communications channels at 868 MHz using the macro-diversity offered by multiple co-located base stations. In this study, ten identical hypothetical base stations were positioned equidistantly around the perimeter of a rectangle of length 6.67 m and width 3.3 m. A body worn node was placed on the central chest region of an adult male. Five scenarios, each considering different user trajectories, were then analyzed to test the efficacy of using macro-diversity when the desired link is subject to shadowing caused by the human body. A number of selection combining based macro-diversity configurations consisting of four and then ten base stations were considered. It was found that using a macro-diversity system consisting of four base stations (or equivalently signal branches), a maximum diversity gain of 22.5 dB could be obtained while implementing a 10-base station setup this figure could be improved to 25.2 dB.

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Parasitism is hypothesized to reduce reproductive success in heavily parasitized males because females
may preferentially mate with less parasitized males (parasite-mediated sexual selection) or parasites may compromise
male competitiveness. In marine systems, this hypothesis is largely unexplored. This paper provides the first confirmed record of a copepod ectoparasite (Caligus buechlerae Hewitt 1964) on the common triplefin (Forsterygion lapillum) and evaluates the hypothesis that males parasitized with C. buechlerae experience lower reproductive success than unparasitized males (as determined
by the presence and area of eggs within male nests). We found that 38 % of males we surveyed were infected with
at least one C. buechlerae, with a median of two individuals per infected male. About 32 % of males were defending
eggs, with 62.5 % of those males infected with at least one parasite. Males of greater total length (TL) were both
more likely to be infected and more likely to be defending eggs. However, when statistically accounting for the effects
of TL, parasite infection had no effect on the probability of defending eggs, or the average surface area of eggs when
present. Positive covariation in fish length, the presence of eggs and parasite infection observed here potentially suggest
that the importance of parasitic infection on reproductive success may depend upon the strength of selection for larger male body size. Our study is one of the few studies to investigate the effects of ectoparasites on reproductive success in reef fish and also provides a quantitative measure of infection for a widespread species within New Zealand.

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This chapter reviews the recent observations of waves and oscillations manifesting in fine-scale magnetic structures in the solar photosphere, which are often interpreted as the "building blocks' of the magnetic Sun. The authors found, through phase relationships between the various waveforms, that small-scale magnetic bright points (MBPs) in the photosphere demonstrated signatures of specific magnetoacoustic waves, in particular the sausage and kink modes. Modern magnetohydrodynamic (MHD) simulations of the lower solar atmosphere clearly show how torsional motions can easily be induced in magnetic elements in the photosphere through the processes of vortical motions and/or buffeting by neighboring granules. The authors detected significant power associated with high-frequency horizontal motions, and suggested that these cases may be especially important in the creation of a turbulent environment that efficiently promotes Alfvén wave dissipation.

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Passive intermodulation (PIM) often limits the performance of communication systems with analog and digitally-modulated signals and especially of systems supporting multiple carriers. Since the origins of the apparently multiple physical sources of nonlinearity causing PIM are not fully understood, the behavioral models are frequently used to describe the process of PIM generation. In this paper a polynomial model of memoryless nonlinearity is deduced from PIM measurements of a microstrip line with distributed nonlinearity with two-tone CW signals. The analytical model of nonlinearity is incorporated in Keysight Technology’s ADS simulator to evaluate the metrics of signal fidelity in the receive band for analog and digitally-modulated signals. PIM-induced distortion and cross-band interference with modulated signals are compared to those with two-tone CW signals. It is shown that conventional metrics can be applied to quantify the effect of distributed nonlinearities on signal fidelity. It is found that the two-tone CW test provides a worst-case estimate of cross-band interference for two-carrier modulated signals whereas with a three-carrier signal PIM interference in the receive band is noticeably overestimated. The simulated constellation diagrams for QPSK signals demonstrate that PIM interference exhibits the distinctive signatures of correlated distortion and this indicates that there are opportunities for mitigating PIM interference and that PIM interference cannot be treated as noise. One of the interesting results is that PIM distortion on a transmission line results in asymmetrical regrowth of output PIM interference for modulated signals.

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BACKGROUND: Particulate matter has been shown to stimulate the innate immune system and induce acute inflammation. Therefore, while nanotechnology has the potential to provide therapeutic formulations with improved efficacy, there are concerns such pharmaceutical preparations could induce unwanted inflammatory side effects. Accordingly, we aim to examine the utility of using the proteolytic activity signatures of cysteine proteases, caspase 1 and cathepsin S (CTSS), as biomarkers to assess particulate-induced inflammation.

METHODS: Primary peritoneal macrophages and bone marrow-derived macrophages from C57BL/6 mice and ctss(-/-) mice were exposed to micro- and nanoparticulates and also the lysosomotropic agent, L-leucyl-L-leucine methyl ester (LLOME). ELISA and immunoblot analyses were used to measure the IL-1β response in cells, generated by lysosomal rupture. Affinity-binding probes (ABPs), which irreversibly bind to the active site thiol of cysteine proteases, were then used to detect active caspase 1 and CTSS following lysosomal rupture. Reporter substrates were also used to quantify the proteolytic activity of these enzymes, as measured by substrate turnover.

RESULTS: We demonstrate that exposure to silica, alum and polystyrene particulates induces IL-1β release from macrophages, through lysosomal destabilization. IL-1β secretion positively correlated with an increase in the proteolytic activity signatures of intracellular caspase 1 and extracellular CTSS, which were detected using ABPs and reporter substrates. Interestingly IL-1β release was significantly reduced in primary macrophages from ctss(-/-) mice.

CONCLUSIONS: This study supports the emerging significance of CTSS as a regulator of the innate immune response, highlighting its role in regulating IL-1β release. Crucially, the results demonstrate the utility of intracellular caspase 1 and extracellular CTSS proteolytic activities as surrogate biomarkers of lysosomal rupture and acute inflammation. In the future, activity-based detection of these enzymes may prove useful for the real-time assessment of particle-induced inflammation and toxicity assessment during the development of nanotherapeutics.