4,966 research outputs found
Lateral vegetation growth rates exert control on coastal foredune hummockiness and coalescing time
Coastal foredunes form along sandy, low-sloped coastlines and range in shape from continuous dune ridges to hummocky features, which are characterized by alongshore-variable dune crest elevations. Initially scattered dune-building plants and species that grow slowly in the lateral direction have been implicated as a cause of foredune hummockiness . Our goal in this work is to explore how the initial configuration of vegetation and vegetation growth characteristics control the development of hummocky coastal dunes including the maximum hummockiness of a given dune field. We find that given sufficient time and absent external forcing, hummocky foredunes coalesce to form continuous dune ridges. Model results yield a predictive rule for the timescale of coalescing and the height of the coalesced dune that depends on initial plant dispersal and two parameters that control the lateral and vertical growth of vegetation, respectively. Our findings agree with previous observational and conceptual work - whether or not hummockiness will be maintained depends on the timescale of coalescing relative to the recurrence interval of high-water events that reset dune building in low areas between hummocks. Additionally, our model reproduces the observed tendency for foredunes to be hummocky along the southeast coast of the US where lateral vegetation growth rates are slower and thus coalescing times are likely longer
Reappraising Threat: How to Optimize Performance Under Pressure
Competitive situations often hinge on one pressurized moment. In these situations, individuals' psychophysiological states determine performance, with a challenge state associated with better performance than a threat state. But what can be done if an individual experiences a threat state? This study examined one potential solution: arousal reappraisal. Fifty participants received either arousal reappraisal or control instructions before performing a pressurized, single-trial, motor task. Although both groups initially displayed cardiovascular responses consistent with a threat state, the reappraisal group displayed a cardiovascular response more reflective of a challenge state (relatively higher cardiac output and/or lower total peripheral resistance) after the reappraisal manipulation. Furthermore, despite performing similarly at baseline, the reappraisal group outperformed the control group during the pressurized task. The results demonstrate that encouraging individuals to interpret heightened physiological arousal as a tool that can help maximize performance can result in more adaptive cardiovascular responses and motor performance under pressure
Enrichment of clinically relevant organisms in spontaneous preterm delivered placenta and reagent contamination across all clinical groups in a large UK pregnancy cohort.
In this study differences in the placental microbiota of term and preterm deliveries from a large UK pregnancy cohort were studied using 16S targeted amplicon sequencing. The impact of contamination from DNA extraction, PCR reagents, as well as those from delivery itself were also examined. A total of 400 placental samples from 256 singleton pregnancies were analysed and differences investigated between spontaneous preterm, non-spontaneous preterm, and term delivered placenta. DNA from recently delivered placenta was extracted, and screening for bacterial DNA was carried out using targeted sequencing of the 16S rRNA gene on the Illumina MiSeq platform. Sequenced reads were analysed for presence of contaminating operational taxonomic units (OTUs) identified via sequencing of negative extraction and PCR blank samples. Differential abundance and between sample (beta) diversity metrics were then compared. A large proportion of the reads sequenced from the extracted placental samples mapped to OTUs that were also found in negative extractions. Striking differences in the composition of samples were also observed, according to whether the placenta was delivered abdominally or vaginally, providing strong circumstantial evidence for delivery contamination as an important contributor to observed microbial profiles. When OTU and genus level abundances were compared between the groups of interest, a number of organisms were enriched in the spontaneous preterm cohort, including organisms that have been previously associated with adverse pregnancy outcomes, specifically Mycoplasma spp., and Ureaplasma spp.. However, analyses of overall community structure did not reveal convincing evidence for the existence of a reproducible 'preterm placental microbiome'.
IMPORTANCE:
Preterm birth is associated with both psychological and physical disabilities and is the leading cause of infant morbidity and mortality worldwide. Infection is known to be an important cause of spontaneous preterm birth, and recent research has implicated variation in the 'placental microbiome' with preterm birth risk. Consistent with previous studies, the abundance of certain clinically relevant species differed between spontaneous preterm and non-spontaneous preterm or term delivered placenta. These results support the view that a proportion of spontaneous preterm births have an intra-uterine infection component. However, an additional observation from this study was that a substantial proportion of reads sequenced were contaminating reads, rather than DNA from endogenous, clinically relevant species. This observation warrants caution in the interpretation of sequencing output from such low biomass samples as the placenta
Pregabalin in fibromyalgia - responder analysis from individual patient data
<p>Abstract</p> <p>Background</p> <p>Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.</p> <p>Methods</p> <p>We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.</p> <p>Results</p> <p>Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.</p> <p>Conclusions</p> <p>Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.</p
Reducing false-positive biopsies: a pilot study to reduce benign biopsy rates for BI-RADS 4A/B assessments through testing risk stratification and new thresholds for intervention
The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84–0.99) (p < 0.001), 0.81 (95 % CI 0.69–0.93) (p = 0.011), and 0.89 (95 % CI 0.83–0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies
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A creative nonfiction story of male elite athletes’ experiences of lifetime stressor exposure, performance, and help-seeking behaviors
Greater lifetime stressor exposure has been related to negative health outcomes (e.g., depression, cardiovascular disease). However, the relationship between lifetime stressor exposure and sporting performance is less clear. Furthermore, while the prevalence of mental health issues among elite athletes has been relatively well established, it appears that sport performers are not effectively utilizing mental health support services, particularly male athletes. Therefore, this study explored male elite athletes’ experiences of lifetime stressor exposure and performance in their sport, as well as their perceptions of the factors influencing mental health help-seeking behavior. Nine elite male athletes (Mage = 27.44 years; SD = 3.50) participated in semistructured interviews (Mduration = 90.25 min, SD = 26.38) supplemented with photo elicitation. Interpretative phenomenological analysis developed group experiential themes. From these themes, we constructed two composite vignettes that addressed each of the research questions, respectively. The first vignette was written using a first-person narrative, allowing the reader to understand an athlete’s (i.e., Toby’s) internal thoughts and feelings, as well as his experiences with lifetime stressors and how they impacted his performance. The second vignette was written using a third-person omniscient narration (i.e., the all-knowing narrator), detailing two athletes’ (i.e., James and Mark’s) experiences of seeking help for mental ill-health. Collectively, the findings offer vital and accessible information that sporting organizations can use to develop collaborative multilevel interventions that better support elite athletes’ performance and mental health, particularly athletes who have experienced greater lifetime stressor exposure
N=2 Instanton Effective Action in Omega-background and D3/D(-1)-brane System in R-R Background
We study the relation between the ADHM construction of instantons in the
Omega-background and the fractional D3/D(-1)-branes at the orbifold singularity
of C \times C^2/Z_2 in Ramond-Ramond (R-R) 3-form field strength background. We
calculate disk amplitudes of open strings connecting the D3/D(-1)-branes in
certain R-R background to obtain the D(-1)-brane effective action deformed by
the R-R background. We show that the deformed D(-1)-brane effective action
agrees with the instanton effective action in the Omega-background.Comment: 35 pages, no figures, references adde
Mutation-Independent Allele-Specific Editing by CRISPR-Cas9, a Novel Approach to Treat Autosomal Dominant Disease
CRISPR-Cas9 provides a tool to treat autosomal dominant disease by non-homologous end joining (NHEJ) gene disruption of the mutant allele. In order to discriminate between wild-type and mutant alleles, Streptococcus pyogenes Cas9 (SpCas9) must be able to detect a single nucleotide change. Allele-specific editing can be achieved by using either a guide-specific approach, in which the missense mutation is found within the guide sequence, or a protospacer-adjacent motif (PAM)-specific approach, in which the missense mutation generates a novel PAM. While both approaches have been shown to offer allele specificity in certain contexts, in cases where numerous missense mutations are associated with a particular disease, such as TGFBI (transforming growth factor β-induced) corneal dystrophies, it is neither possible nor realistic to target each mutation individually. In this study, we demonstrate allele-specific CRISPR gene editing independent of the disease-causing mutation that is capable of achieving complete allele discrimination, and we propose it as a targeting approach for autosomal dominant disease. Our approach utilizes natural variants in the target region that contain a PAM on one allele that lies in cis with the causative mutation, removing the constraints of a mutation-dependent approach. Our innovative patient-specific guide design approach takes into account the patient’s individual genetic make-up, allowing on- and off-target activity to be assessed in a personalized manner
RAD sequencing resolves fine-scale population structure in a benthic invertebrate: implications for understanding phenotypic plasticity.
The field of molecular ecology is transitioning from the use of small panels of classical genetic markers such as microsatellites to much larger panels of single nucleotide polymorphisms (SNPs) generated by approaches like RAD sequencing. However, few empirical studies have directly compared the ability of these methods to resolve population structure. This could have implications for understanding phenotypic plasticity, as many previous studies of natural populations may have lacked the power to detect genetic differences, especially over micro-geographic scales. We therefore compared the ability of microsatellites and RAD sequencing to resolve fine-scale population structure in a commercially important benthic invertebrate by genotyping great scallops (Pecten maximus) from nine populations around Northern Ireland at 13 microsatellites and 10 539 SNPs. The shells were then subjected to morphometric and colour analysis in order to compare patterns of phenotypic and genetic variation. We found that RAD sequencing was superior at resolving population structure, yielding higher Fst values and support for two distinct genetic clusters, whereas only one cluster could be detected in a Bayesian analysis of the microsatellite dataset. Furthermore, appreciable phenotypic variation was observed in size-independent shell shape and coloration, including among localities that could not be distinguished from one another genetically, providing support for the notion that these traits are phenotypically plastic. Taken together, our results suggest that RAD sequencing is a powerful approach for studying population structure and phenotypic plasticity in natural populations
MMS observations of electron-scale filamentary currents in the reconnection exhaust and near the X line
© 2016. American Geophysical Union. All Rights Reserved.We report Magnetospheric Multiscale observations of macroscopic and electron-scale current layers in asymmetric reconnection. By intercomparing plasma, magnetic, and electric field data at multiple crossings of a reconnecting magnetopause on 22 October 2015, when the average interspacecraft separation was ~10km, we demonstrate that the ion and electron moments are sufficiently accurate to provide reliable current density measurements at 30ms cadence. These measurements, which resolve current layers narrower than the interspacecraft separation, reveal electron-scale filamentary Hall currents and electron vorticity within the reconnection exhaust far downstream of the X line and even in the magnetosheath. Slightly downstream of the X line, intense (up to 3μA/m2) electron currents, a super-Alfvénic outflowing electron jet, and nongyrotropic crescent shape electron distributions were observed deep inside the ion-scale magnetopause current sheet and embedded in the ion diffusion region. These characteristics are similar to those attributed to the electron dissipation/diffusion region around the X line
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