Somatic CLL mutations occur at multiple distinct hematopoietic maturation stages: documentation and cautionary note regarding cell fraction purity.
Ontology highlight
ABSTRACT:
SUBMITTER: Marsilio S
PROVIDER: S-EPMC5886053 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Somatic CLL mutations occur at multiple distinct hematopoietic maturation stages: documentation and cautionary note regarding cell fraction purity.
Marsilio S S Khiabanian H H Fabbri G G Vergani S S Scuoppo C C Montserrat E E Shpall E J EJ Hadigol M M Marin P P Rai K R KR Rabadan R R Devereux S S Pasqualucci L L Chiorazzi N N
Leukemia 20171205 4
Similar Datasets
Project description:BackgroundAlcohol consumption is commonly used as a primary outcome in randomized alcohol treatment studies. The distribution of alcohol consumption is highly skewed, particularly in subjects with alcohol dependence.MethodsIn this paper, we will consider the use of count models for outcomes in a randomized clinical trial setting. These include the Poisson, over-dispersed Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial. We compare the Type-I error rate of these methods in a series of simulation studies of a randomized clinical trial, and apply the methods to the ASAP (Addressing the Spectrum of Alcohol Problems) trial.ResultsStandard Poisson models provide a poor fit for alcohol consumption data from our motivating example, and did not preserve Type-I error rates for the randomized group comparison when the true distribution was over-dispersed Poisson. For the ASAP trial, where the distribution of alcohol consumption featured extensive over-dispersion, there was little indication of significant randomization group differences, except when the standard Poisson model was fit.ConclusionAs with any analysis, it is important to choose appropriate statistical models. In simulation studies and in the motivating example, the standard Poisson was not robust when fit to over-dispersed count data, and did not maintain the appropriate Type-I error rate. To appropriately model alcohol consumption, more flexible count models should be routinely employed.
| S-EPMC1810542 | biostudies-literature
Project description:Models based on the Ornstein-Uhlenbeck process have become standard for the comparative study of adaptation. Cooper et al. (2016) have cast doubt on this practice by claiming statistical problems with fitting Ornstein-Uhlenbeck models to comparative data. Specifically, they claim that statistical tests of Brownian motion may have too high Type I error rates and that such error rates are exacerbated by measurement error. In this note, we argue that these results have little relevance to the estimation of adaptation with Ornstein-Uhlenbeck models for three reasons. First, we point out that Cooper et al. (2016) did not consider the detection of distinct optima (e.g. for different environments), and therefore did not evaluate the standard test for adaptation. Second, we show that consideration of parameter estimates, and not just statistical significance, will usually lead to correct inferences about evolutionary dynamics. Third, we show that bias due to measurement error can be corrected for by standard methods. We conclude that Cooper et al. (2016) have not identified any statistical problems specific to Ornstein-Uhlenbeck models, and that their cautions against their use in comparative analyses are unfounded and misleading. [adaptation, Ornstein-Uhlenbeck model, phylogenetic comparative method.].
| S-EPMC10405355 | biostudies-literature
Project description:We examine the effects of multiple sources of noise in risky decision making. Noise in the parameters that characterize an individual's preferences can combine with noise in the response process to distort observed choice proportions. Thus, underlying preferences that conform to expected value maximization can appear to show systematic risk aversion or risk seeking. Similarly, core preferences that are consistent with expected utility theory, when perturbed by such noise, can appear to display nonlinear probability weighting. For this reason, modal choices cannot be used simplistically to infer underlying preferences. Quantitative model fits that do not allow for both sorts of noise can lead to wrong conclusions. (PsycINFO Database Record
| S-EPMC5619393 | biostudies-literature
Project description:The article tackles the practice of testing latent variable models. The analysis covered recently published studies from 11 psychology journals varying in orientation and impact. Seventy-five studies that matched the criterion of applying some of the latent modeling techniques were reviewed. Results indicate the presence of a general tendency to ignore the model test (χ(2)) followed by the acceptance of approximate fit hypothesis without detailed model examination yielding relevant empirical evidence. Due to reduced sensitivity of such a procedure to confront theory with data, there is an almost invariable tendency to accept the theoretical model. This absence of model test consequences, manifested in frequently unsubstantiated neglect of evidence speaking against the model, thus implies the perilous question of whether such empirical testing of latent structures (the way it is widely applied) makes sense at all.
| S-EPMC4635201 | biostudies-literature
Project description:Primary rodent astroglial-enriched cultures are the most popular model to study astroglial biology in vitro. From the original methods described in the 1970's a great number of minor modifications have been incorporated into these protocols by different laboratories. These protocols result in cultures in which the astrocyte is the predominant cell type, but astrocytes are never 100% of cells in these preparations. The aim of this review is to bring attention to the presence of microglia in astroglial cultures because, in my opinion, the proportion of and the role that microglial cells play in astroglial cultures are often underestimated. The main problem with ignoring microglia in these cultures is that relatively minor amounts of microglia can be responsible for effects observed on cultures in which the astrocyte is the most abundant cell type. If the relative contributions of astrocytes and microglia are not properly assessed an observed effect can be erroneously attributed to the astrocytes. In order to illustrate this point the case of NO production in activated astroglial-enriched cultures is examined. Lipopolysaccharide (LPS) induces nitric oxide (NO) production in astroglial-enriched cultures and this effect is very often attributed to astrocytes. However, a careful review of the published data suggests that LPS-induced NO production in rodent astroglial-enriched cultures is likely to be mainly microglial in origin. This review considers cell culture protocol factors that can affect the proportion of microglial cells in astroglial cultures, strategies to minimize the proportion of microglia in these cultures, and specific markers that allow the determination of such microglial proportions.
| S-EPMC2140055 | biostudies-literature
Project description:Purpose Reproducibility of scientific experimentation has become a major concern because of the perception that many published biomedical studies cannot be replicated. In this article, we draw attention to the connection between inflated overoptimistic findings and the use of cross-validation for error estimation in molecular classification studies. We show that, in the absence of careful design to prevent artifacts caused by systematic differences in the processing of specimens, established tools such as cross-validation can lead to a spurious estimate of the error rate in the overoptimistic direction, regardless of the use of data normalization as an effort to remove these artifacts. Methods We demonstrated this important yet overlooked complication of cross-validation using a unique pair of data sets on the same set of tumor samples. One data set was collected with uniform handling to prevent handling effects; the other was collected without uniform handling and exhibited handling effects. The paired data sets were used to estimate the biologic effects of the samples and the handling effects of the arrays in the latter data set, which were then used to simulate data using virtual rehybridization following various array-to-sample assignment schemes. Results Our study showed that (1) cross-validation tended to underestimate the error rate when the data possessed confounding handling effects; (2) depending on the relative amount of handling effects, normalization may further worsen the underestimation of the error rate; and (3) balanced assignment of arrays to comparison groups allowed cross-validation to provide an unbiased error estimate. Conclusion Our study demonstrates the benefits of balanced array assignment for reproducible molecular classification and calls for caution on the routine use of data normalization and cross-validation in such analysis.
| S-EPMC5477984 | biostudies-literature
Project description:Accurate and detailed documentation of surgical procedures is part of good clinical practice, set out by the General Medical Council (GMC). Knee arthroscopy often involves large data sets which require accurate documentation for future assessment and management. This study assesses the quality of documentation of knee arthroscopy, followed by an evaluation of the implementation of a novel operative proforma. A review of 30 consecutive knee arthroscopy operation notes were analysed for missing information, set against a standardised 30 point criteria. An operation proforma was then introduced, and a further 30 consecutive knee arthroscopy operation notes were analysed. We evaluated allied health professional satisfaction with a Likert point scale survey of 21 allied healthcare professionals (recovery and ward nurses, and physiotherapists) following introduction of the proforma. The mean number of missing items on a 30 point scale was 8.8 (range 0 to 23). Examination under anaesthesia was missed in 43% of cases, tourniquet time in 37% of cases, and wear results in 17% of cases. Following introduction of the proforma, the mean number of missing items was 1.1 (range 0 to 24; p <0.001). This rose to 3.8 after one year (p <0.001) before improvement to 0.7 (p <0.01) with a new and improved proforma. Eighty percent strongly agreed the operation note was clearer, 90% strongly agreed it was more legible, 90% strongly agreed it was more understandable, 50% strongly agreed there was more information recorded, and 100% strongly agreed on the proforma having been improved. Knee arthroscopy is a common procedure with large data sets, which can often be missed or incomplete. A standardised proforma results in a statistically significant improvement in documentation and reduces the incidence of missing information. They are subjectively clearer, more legible, and generally better compared with handwritten notes. This study demonstrates the improvements in healthcare documentation, both clinically and legally, following introduction of a simple proforma. This concept should be applicable to different specialities and procedures in healthcare.
| S-EPMC4752707 | biostudies-literature
Project description:Tacrolimus is a core component of immunosuppressive regimens. This study compared active pharmaceutical ingredient (API) and dissolution kinetics of branded tacrolimus and formulations from three generic manufacturers (Mylan, Dr. Reddy's, Intas) including samples from patients who suffered acute cardiac allograft rejection. Generic samples showed similar API content compared to branded samples with no major impurities. Capsules that underwent uniformity testing had consistent capsule-to-capsule API. Dissolution testing showed similar profiles between branded tacrolimus and Mylan, but notable differences with Dr. Reddy's and Intas. The approximate maximal inhibitory concentration (IC50) was highest in branded tacrolimus (29 minutes), followed by Mylan (26 minutes), Dr. Reddy's (19 minutes), and Intas (14 minutes) (Student-Newman-Keuls Multiple Comparisons Test; overall ANOVA: p = 0.0199, F = 6.469). This study suggests that the bioavailability of certain generic tacrolimus formulations peak significantly earlier than branded tacrolimus. Further study is needed to determine whether these differences are clinically relevant.
| S-EPMC10257977 | biostudies-literature
Project description:IntroductionRadiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA).MethodsWe undertook neuropathological examination of 65 older people (81.6 ± 7.96 (mean ± SD) years, 27F/38M): 15 with neuropathological diagnosis of AD, 25 with neuropathological diagnosis of other neurodegenerative dementias (Lewy body dementia and Parkinson disease dementia), and 25 without significant neurodegenerative pathology.ResultsWe observed CAA in non-Alzheimer's dementia (non-AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aβ-positive vessel density did not differ significantly between non-AD dementia and control groups. Across all subjects there was a highly significant correlation between vessel Aβ40 density and vessel Aβ42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups.ConclusionOur data indicate that CAA can be abundant in non-AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.
| S-EPMC7885797 | biostudies-literature
Project description: Not available
| S-EPMC11438546 | biostudies-literature