993 resultados para Potter, Beattie


Relevância:

10.00% 10.00%

Publicador:

Resumo:

<p>Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (&lt;1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.</p>

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Background: Spatially localized duration compression of a briefly presented moving stimulus following adaptation in the same location is taken as evidence for modality-specific neural timing mechanisms. <br/><br/>Aims: The present study used random dot motion stimuli to investigate where these mechanisms may be located. <br/><br/>Method: Experiment 1 measured duration compression of the test stimulus as a function of adaptor speed and revealed that duration compression is speed tuned. These data were then used to make predictions of duration compression responses for various models which were tested in experiment 2. Here a mixed-speed adaptor stimulus was used with duration compression being measured as a function of the adaptorâs â˜speed notchâ (the removal of a central band from the speed range). <br/><br/>Results: The results were consistent with a local-mean model. <br/><br/>Conclusions: Local-motion mechanisms are involved in duration perception of brief events.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Accurately encoding the duration and temporal order of events is essential for survival and important to everyday activities, from holding conversations to driving in fast flowing traffic. Although there is a growing body of evidence that the timing of brief events (&lt; 1s) is encoded by modality-specific mechanisms, it is not clear how such mechanisms register event duration. One approach gaining traction is a channel-based model; this envisages narrowly-tuned, overlapping timing mechanisms that respond preferentially to different durations. The channel-based model predicts that adapting to a given event duration will result in overestimating and underestimating the duration of longer and shorter events, respectively. We tested the model by having observers judge the duration of a brief (600ms) visual test stimulus following adaptation to longer (860ms) and shorter (340ms) stimulus durations. The channel-based model predicts perceived duration compression of the test stimulus in the former condition and perceived duration expansion in the latter condition. Duration compression occurred in both conditions, suggesting that the channel-based model does not adequately account for perceived duration of visual events.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Processos e Modelos de Raciocínio na Tomada de Decisão: contributos concetuais e interrogações Dulce Magalhães - Departamento de Enfermagem, Universidade de Ãvora Manuel Lopes - Departamento de Enfermagem, Universidade de Ãvora Ana Fonseca - Departamento de Enfermagem, Universidade de Ãvora Os enfermeiros que integram as equipas de unidades de cuidados hospitalares têm que prevenir, minimizar e corrigir situações clínicas instáveis. Em consequência disso defrontam-se diária e sistematicamente com a obrigatoriedade de tomar decisões no contexto da ação (Thompson & Dowding, 2005) e agir em conformidade. Eles têm que tomar decisões num espaço que não é reservado e que está confinado a uma teia de relações que acontecem entre o doente, a família e os restantes membros da equipa de saúde (Benner et al, 2011; Tanner, 2006, Lopes, 2006). Um espaço onde acontecem múltiplas interrupções que provêm de procedimentos de trabalho e exigências constantes de atenção a cada doente (Hedberg & Larsson, 2004; Potter et al, 2005; Wolf et al, 2006). São decisões processuais e multidimensionais que têm que considerar em simultâneo, o que deve ser feito, como deve ser feito e quando deve ser feito, no respeito da singularidade do doente e do seu contexto circundante (Gillespie, 2009). Esta dinâmica também está interligada com os dados clínicos que recorrentemente emergem, bem como à acessibilidade, multiplicidade e ambiguidade dos dados clínicos (Junnola et al, 2002; Carnevali &Thomas, 1993 Simmons, 2010), ao tempo de decisão e às decisões conflituosas (Thompson, 2004). São ambientes clínicos onde acontecem contingências, algumas delas aleatórias, que exigem que os enfermeiros independentemente dos níveis de proficiência sejam obrigados a tomar decisões complexas de forma rápida e precisa, para optimizar os resultados esperados (Curry & Botti, 2006). O conhecimento e o raciocínio que os enfermeiros usam na tomada de decisão são elementos, entre outros, que definem muito da prática profissional (Cody, 2006). Por isso, conscientes da realidade enunciada através da investigação que tem vindo a ser desenvolvida, foi nossa intenção analisar criticamente os modelos de decisão que têm expressão na literatura de enfermagem e que têm sido desenvolvidos em diferentes áreas do conhecimento (Concoran-Perry et al, 1999), no sentido de reconhecer o seu poder explicativo para a tomada de decisão dos enfermeiros. Alguns deles são apresentados numa estrutura normativa, outros numa descritiva e em função disso, podem dividir-se em duas categorias teóricas, sistemático-positivista e intuitivo-humanista (Thompson, 1999; Aitken, Marshall, Elliott & McKinley, 2007). As abordagens sistemático-positivistas sugerem que a tomada de decisão acontece num processo sequencial previamente definido e explicitado. Assentam no pressuposto que existe alguma atividade de análise ou de resolução de problemas em curso, para o enfermeiro tomar uma decisão. Nas abordagens intuitivo-humanistas a decisão é entendida no seio de um processo como um todo e no contexto de uma abordagem naturalista (Benner, 1984; Thompson, 1999). Elas podem ser diferenciadas, desde logo, a partir dos seus centros de interesse. Enquanto a primeira se interessa pelo número de dados e pelos processos de análise cognitiva para uma melhor decisão. A segunda dá primazia aos contextos relacionais e de comunicação com os doentes e serve-se da performance clínica para eleger as melhores ações.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

In the hotel industry, undistributed operating expenses represent a significant portion of the operating costs for a hotel. Exactly how most of these expenses arise is not well understood. Using data from more than 40 hotels operated by a major chain, the authors examine the links between the variety of a hotelâs products and customers and its undistributed operating expenses and revenues. Their findings show that undistributed operating expenses are related to the extent of the propertyâs business and product-services mix. The results suggest that although increasing a property's product-service mix results in higher undistributed operating expenses, the incremental costs are compensated for by higher revenues. However, increasing business mix while increasing undistributed operating expenses does not result in higher revenues.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Making more money involves more than targeting new customer segments and offering new services.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

This paper reports on the financial impacts from the termination of a pay for performance plan for the salesforce at a retail establishment. Using monthly panel data spanning more than eight years for 15 outlets of a major retailer, this study documents that store-level sales and operating profits decrease after the incentive plan is terminated. Individual performance data are then investigated to help identify the role of effort and selection effects in explaining the documented decrease. The analysis of the individual employee sales data reveals that virtually all of the declining store level sales can be explained by selection effects.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Tese de doutoramento, e-Planeamento, Universidade de Lisboa, Faculdade de Ciências, Universidade Nova de Lisboa, Universidade de Aveiro, 2015

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (PâŠ=âŠ4.5Ã10(-8)-1.2Ã10(-43)). Using a novel method to combine data across ethnicities (NâŠ=âŠ4,232 African Americans, NâŠ=âŠ1,776 Asians, and NâŠ=âŠ29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p&lt;3Ã10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (pâŠ=âŠ4.3Ã10(-3), nâŠ=âŠ22,044), increased triglycerides (pâŠ=âŠ2.6Ã10(-14), nâŠ=âŠ93,440), increased waist-to-hip ratio (pâŠ=âŠ1.8Ã10(-5), nâŠ=âŠ77,167), increased glucose two hours post oral glucose tolerance testing (pâŠ=âŠ4.4Ã10(-3), nâŠ=âŠ15,234), increased fasting insulin (pâŠ=âŠ0.015, nâŠ=âŠ48,238), but with lower in HDL-cholesterol concentrations (pâŠ=âŠ4.5Ã10(-13), nâŠ=âŠ96,748) and decreased BMI (pâŠ=âŠ1.4Ã10(-4), nâŠ=âŠ121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P &lt; 5 à 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value &lt;0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P &lt; 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.