400 research outputs found

    Interaction of perceptual grouping and crossmodal temporal capture in tactile apparent-motion

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    Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can "capture'' visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left-or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from -75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs-one short (75 ms), one long (325 ms)-were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects

    TRATAMENTO FARMACOLÓGICO E NÃO FARMACOLÓGICO NO MANEJO DA DOR DE PACIENTES EM PÓS-OPERATÓRIO IMEDIATO (POI)

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    O objetivo deste estudo foi analisar evidências científicas referentes às modalidades farmacológicas e não farmacológicas utilizadas no manejo da dor de pacientes em Pós-Operatório Imediato (POI) de cirurgias em geral. Este é uma revisão integrativa da literatura realizada nas bases LILACS, MEDLINE/PUBMED, Scopus e Web of Science, entre 2002 e 2017, que resultou na análise de 38 artigos científicos. Dos artigos analisados, 71% abordaram métodos farmacológicos e 28% medidas não farmacológicas para o tratamento da dor no POI. O manejo adequado da dor é de responsabilidade dos profissionais envolvidos no cuidado e os hospitais devem ter equipes e procedimentos para alívio da dor para diminuir efeitos colaterais, tempo de hospitalização e acelerar a recuperação do paciente. Os métodos não farmacológicos podem ser uma modalidade complementar promissora para melhorar a dor no pós-operatório, pois são técnicas acessíveis e fáceis de serem executadas e quando praticada por profissionais capacitados, os eventos adversos ocorrem raramente

    Integrated Assessment of Genomic Correlates of Protein Evolutionary Rate

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    Rates of evolution differ widely among proteins, but the causes and consequences of such differences remain under debate. With the advent of high-throughput functional genomics, it is now possible to rigorously assess the genomic correlates of protein evolutionary rate. However, dissecting the correlations among evolutionary rate and these genomic features remains a major challenge. Here, we use an integrated probabilistic modeling approach to study genomic correlates of protein evolutionary rate in Saccharomyces cerevisiae. We measure and rank degrees of association between (i) an approximate measure of protein evolutionary rate with high genome coverage, and (ii) a diverse list of protein properties (sequence, structural, functional, network, and phenotypic). We observe, among many statistically significant correlations, that slowly evolving proteins tend to be regulated by more transcription factors, deficient in predicted structural disorder, involved in characteristic biological functions (such as translation), biased in amino acid composition, and are generally more abundant, more essential, and enriched for interaction partners. Many of these results are in agreement with recent studies. In addition, we assess information contribution of different subsets of these protein properties in the task of predicting slowly evolving proteins. We employ a logistic regression model on binned data that is able to account for intercorrelation, non-linearity, and heterogeneity within features. Our model considers features both individually and in natural ensembles (“meta-features”) in order to assess joint information contribution and degree of contribution independence. Meta-features based on protein abundance and amino acid composition make strong, partially independent contributions to the task of predicting slowly evolving proteins; other meta-features make additional minor contributions. The combination of all meta-features yields predictions comparable to those based on paired species comparisons, and approaching the predictive limit of optimal lineage-insensitive features. Our integrated assessment framework can be readily extended to other correlational analyses at the genome scale

    Engaging rural preceptors in new longitudinal community clerkships during workforce shortage: a qualitative study

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    Background: In keeping with its mission to produce doctors for rural and regional Australia, the University of Wollongong, Graduate School of Medicine has established an innovative model of clinical education. This includes a 12-month integrated community-based clerkship in a regional or rural setting, offering senior students longitudinal participation in a \u27community of practice\u27 with access to continuity of patient care experiences, continuity of supervision and curriculum, and individualised personal and professional development. This required developing new teaching sites, based on attracting preceptors and providing them with educational and physical infrastructure. A major challenge was severe health workforce shortages. Methods: Before the new clerkship started, we interviewed 28 general practitioners to determine why they engaged as clerkship preceptors. Independent researchers conducted semi-structured interviews. Responses were transcribed for inductive qualitative content analysis. Results: The new model motivated preceptors to engage because it enhanced their opportunities to contribute to authentic learning when compared with the perceived limitations of short-term attachments. Preceptors appreciated the significant recognition of the value of general practice teaching and the honour of major involvement in the university. They predicted that the initiative would have positive effects on general practitioner morale and improve the quality of their practice. Other themes included the doctors\u27 commitment to their profession, \u27handing on\u27 to the next generation and helping their community to attract doctors in the future. Conclusions: Supervisors perceive that new models of clinical education offer alternative solutions to health care education, delivery and workforce. The longitudinal relationship between preceptor, student and community was seen as offering reciprocal benefits. General practitioners are committed to refining practice and ensuring generation of new members in their profession. They are motivated to engage in novel regional and rural longitudinal clinical clerkships as they perceive that they offer students an authentic learning experience and are a potential strategy to help address workforce shortages and maldistribution

    Why Is the Correlation between Gene Importance and Gene Evolutionary Rate So Weak?

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    One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful despite the weakness of the correlation

    Development of a longitudinal integrated clerkship at an academic medical center

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    In 2005, medical educators at the University of California, San Francisco (UCSF), began developing the Parnassus Integrated Student Clinical Experiences (PISCES) program, a year-long longitudinal integrated clerkship at its academic medical center. The principles guiding this new clerkship were continuity with faculty preceptors, patients, and peers; a developmentally progressive curriculum with an emphasis on interdisciplinary teaching; and exposure to undiagnosed illness in acute and chronic care settings. Innovative elements included quarterly student evaluation sessions with all preceptors together, peer-to-peer evaluation, and oversight advising with an assigned faculty member. PISCES launched with eight medical students for the 2007/2008 academic year and expanded to 15 students for 2008/2009. Compared to UCSF's traditional core clerkships, evaluations from PISCES indicated significantly higher student satisfaction with faculty teaching, formal didactics, direct observation of clinical skills, and feedback. Student performance on discipline-specific examinations and United States Medical Licensing Examination step 2 CK was equivalent to and on standardized patient examinations was slightly superior to that of traditional peers. Participants' career interests ranged from primary care to surgical subspecialties. These results demonstrate that a longitudinal integrated clerkship can be implemented successfully at a tertiary care academic medical center

    Structure and Age Jointly Influence Rates of Protein Evolution

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    What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate. We use a large set of one-to-one orthologs between human and mouse proteins, with mapped PDB structures. We report that previously observed structural correlations also hold within each age group – including relationships between solvent accessibility, designabililty, and evolutionary rates. However, age also plays a crucial role: age modulates the relationship between solvent accessibility and rate. Additionally, younger proteins, despite being less designable, tend to evolve faster than older proteins. We show that previously reported relationships between age and rate cannot be explained by structural biases among age groups. Finally, we introduce a knowledge-based potential function to study the stability of proteins through large-scale computation. We find that older proteins are more stable for their native structure, and more robust to mutations, than younger ones. Our results underscore that several determinants, both intrinsic and historical, can interact to determine rates of protein evolution

    Measurement of Warfarin in the Oral Fluid of Patients Undergoing Anticoagulant Oral Therapy

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    BACKGROUND: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls. METHODOLOGY: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm. FINDINGS: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL). Dosage was not correlated to INR (r = -0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004). CONCLUSIONS: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters

    Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo

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    Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I125 CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases
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