1,312 research outputs found

    GP Participation and Recruitment of Patients to RCTs: Lessons from Trials of Acupuncture and Exercise for Low Back Pain in Primary Care

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    The objective of this study was to identify factors associated with general practitioner (GP) participation and the recruitment of people to trials in primary care, based on data from two trials of interventions for treating chronic low back pain. The study was based on data from two randomized controlled trials (RCTs), one involving exercise, the other acupuncture, and subsequent reporting by GPs in a postal questionnaire. The exercise trial achieved 62% recruitment whereas the acupuncture trial achieved 100% recruitment. In both trials GPs most efficient at referring patients were those with a special interest in the subject area, and those known personally to the research team. A follow-up GP questionnaire found that both trials had maintained a high profile with over 80% of GPs, and successful recruitment strategies included project reminder letters, updates and personal contacts. Achieving target recruitment of patients in the acupuncture trial was aided by the deliberate application of lessons learned in the exercise trial, in particular the need to keep initial study entry criteria broad, with subsequent filtering undertaken by the study researcher. In addition the use of effective methods of maintaining the trial profile, the involvement of a GP advisor, the decision to maximize the recruitment of GPs early in the trial and the direct recruitment of interested individual GPs. The successful recruitment of patients to trials in primary care requires careful planning and continuous monitoring from the outset. Prior to starting recruitment, it is useful to identify previous trials in a similar environment in order to learn from their experience and optimize patient recruitment

    Fingerprints of biocomplexity: Taxon‐specific growth of phytoplankton in relation to environmental factors

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110012/1/lno2004494part21446.pd

    PRINCIPAL COMPONENTS ANALYSIS CORRECTS COLLIDER BIAS IN POLYGENIC RISK SCORE EFFECT SIZE ESTIMATION

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    BACKGROUND: Genome-wide polygenic scoring has emerged as a way to predict psychiatric and behavioral outcomes and identify environments that promote the expression of genetic risks. An increasing number of studies demonstrate that the effects of polygenic risk scores (PRS) may be biased by the inclusion of heritable environments as covariates when the environment is influenced by unmeasured confounding variables, an example of collider bias. Inclusion of the principal components of observed confounders as covariates may correct for the effect of unmeasured confounders. METHODS: A simulation study was conducted to test principal components analysis (PCA) as a correction for collider bias. Data were sampled from a model which tested different values for the effect of the polygenic risk score on the heritable environment, the correlation structure of the unmeasured confounding data, and the proportion of the confounding data that is used to construct the principal components. Other model parameters were fixed across all simulation iterations. RESULTS: Modeling the first PC of observed confounders as a covariate recovers the PRS effect size estimate under reasonable assumptions about the proportion of the confounding data that is measured or the correlation structure of the confounding data. Required assumptions become stricter as the effect of PRS on environment (and the magnitude of bias) increases. CONCLUSION: Inclusion of the first PC of observed confounders as a covariate may improve the accuracy of PRS effect size estimation when heritable environments are included in the model as covariates. Future directions include application of this method in observed data.https://scholarscompass.vcu.edu/gradposters/1130/thumbnail.jp

    Purinergic Signaling Controls Spontaneous Activity in the Auditory System throughout Early Development

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    Spontaneous bursts of electrical activity in the developing auditory system arise within the cochlea before hearing onset and propagate through future sound-processing circuits of the brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux, and subsequent depolarization of inner hair cells. However, it is unknown when this activity emerges or whether different mechanisms induce activity during distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea from both sexes emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in inner hair cells and spiral ganglion neurons, which begins at birth and follows a base to apex developmental gradient. At all developmental ages, pharmacological inhibition of P2Y1 purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus revealed that auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea indicate that this efferent input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the auditory system uses a consistent mechanism involving ATP release from ISCs and activation of P2RY1 autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound.Fil: Babola, Travis A.. University Johns Hopkins; Estados UnidosFil: Li, Sally. University Johns Hopkins; Estados UnidosFil: Wang, Zhirong. University Of Georgetown; Estados UnidosFil: Kersbergen, Calvin J.. University Johns Hopkins; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Coate, Thomas M.. University Johns Hopkins; Estados UnidosFil: Bergles, Dwight E.. University Johns Hopkins; Estados Unido

    Implications of increasing Atlantic influence for Arctic microbial community structure

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    Increasing influence of Atlantic water in the Arctic Ocean has the potential to significantly impact regional water temperature and salinity. Here we use a rDNA barcoding approach to reveal how microbial communities are partitioned into distinct assemblages across a gradient of Atlantic-Polar Water influence in the Norwegian Sea. Data suggest that temperate adapted bacteria may replace cold water taxa under a future scenario of increasing Atlantic influence, but the eukaryote response is more complex. Some abundant eukaryotic cold water taxa could persist, while less abundant eukaryotic taxa may be replaced by warmer adapted temperate species. Furthermore, within lineages, different taxa display evidence of increased relative abundance in reaction to favourable conditions and we observed that rare microbial taxa are sample site rather than region specific. Our findings have significant implications for the vulnerability of polar associated community assemblages, which may change, impacting the ecosystem services they provide, under predicted increases of Atlantic mixing and warming within the Arctic region

    p53 and translation attenuation regulate distinct cell cycle checkpoints during endoplasmic reticulum (ER) stress.

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    Cell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G(1) phase, although recent studies have identified a novel ER stress G(2) checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G(2) delay involving CHK1 and a later induction of G(1) arrest associated both with the induction of p53 target genes and loss of cyclin D(1). We show that substitution of p53/47 for p53 impairs the ER stress G(1) checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G(2) progression prior to ultimate G(1) arrest

    Obsessive passion: a dependency associated with injury-related risky behaviour in dancers

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    Grounded in self-determination theory, obsessive passion for an activity has been associated with increased risky behaviour and rigid persistence, both symptomatic of dependence. However, it is unknown whether obsessive passion may predict the development of dependence, and furthermore, theoretically important relationships between basic need satisfaction, passion, exercise dependence and subsequent risky behaviour have not been fully explored. A sample of 100 professional dancers (50fs; 50ms; Mage = 20.88; SD = 2.69) completed self-ratings of risk-related behaviours (doctor visits; following treatment, and warming up), passion for dance and dance dependence. Findings supported the maladaptive nature of obsessive passion in relation to risky behaviour and as predicted dance dependence mediated this relationship. Interestingly, need satisfaction was positively related to both obsessive passion and harmonious passion. Results are discussed in the light of self-determination theory and dysfunctions of obsessive passion, suggesting that professional dancers are at risk of employing maladaptive behaviours if high in obsessive passion, which may be detectable via symptoms of dance dependence

    Networking Practitioners To Impact Teacher Education

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    A description is given of the Regional Partnership Program; a field-responsive; center-specific model established at the University of Northern Iowa; designed to oversee clinical field experiences for student teachers. The model involves six regional districts specifically located across the state which serve as the administrative units for the field program. All of the centers have a common structure to allow for program continuity. Several examples of this continuity include: (1) every center has a tenure track professor who is the administrator for all aspects of the center\u27s operation; (2) all centers have implemented a full semester student teaching curriculum; and (3) all center partnerships have established an advisory cadre of local educational practitioners; consisting of at least five professional educators from regional schools. Individual cadres are free to engage in projects they believe are pertinent to their needs. The center-specific component of this partnership program is designed to encourage creativity to respond to regional needs. Cadre involvement extends beyond clinical field experience activities because cadre members are involved in a variety of teacher education matters. Each regional partnership structures the student teaching clinical field experience in ways that best fit the regional district. (JD
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