Fractal Characterizations of MAX Statistical Distribution in Genetic Association Studies

Two non-integer parameters are defined for MAX statistics, which are maxima of $d$ simpler test statistics. The first parameter, $d_{MAX}$, is the fractional number of tests, representing the equivalent numbers of independent tests in MAX. If the $d$ tests are dependent, $d_{MAX} < d$. The second parameter is the fractional degrees of freedom $k$ of the chi-square distribution $\chi^2_k$ that fits the MAX null distribution. These two parameters, $d_{MAX}$ and $k$, can be independently defined, and $k$ can be non-integer even if $d_{MAX}$ is an integer. We illustrate these two parameters using the example of MAX2 and MAX3 statistics in genetic case-control studies. We speculate that $k$ is related to the amount of ambiguity of the model inferred by the test. In the case-control genetic association, tests with low $k$ (e.g. $k=1$) are able to provide definitive information about the disease model, as versus tests with high $k$ (e.g. $k=2$) that are completely uncertain about the disease model. Similar to Heisenberg's uncertain principle, the ability to infer disease model and the ability to detect significant association may not be simultaneously optimized, and $k$ seems to measure the level of their balance

Fast calibrated additive quantile regression

We propose a novel framework for fitting additive quantile regression models, which provides well calibrated inference about the conditional quantiles and fast automatic estimation of the smoothing parameters, for model structures as diverse as those usable with distributional GAMs, while maintaining equivalent numerical efficiency and stability. The proposed methods are at once statistically rigorous and computationally efficient, because they are based on the general belief updating framework of Bissiri et al. (2016) to loss based inference, but compute by adapting the stable fitting methods of Wood et al. (2016). We show how the pinball loss is statistically suboptimal relative to a novel smooth generalisation, which also gives access to fast estimation methods. Further, we provide a novel calibration method for efficiently selecting the 'learning rate' balancing the loss with the smoothing priors during inference, thereby obtaining reliable quantile uncertainty estimates. Our work was motivated by a probabilistic electricity load forecasting application, used here to demonstrate the proposed approach. The methods described here are implemented by the qgam R package, available on the Comprehensive R Archive Network (CRAN)

Reliability of miRNA Analysis from Fixed and Paraffin-Embedded Tissues

In clinical practice, patients\u2019 tissues are fixed and paraffin-embedded in order to enable histological diagnosis. Nowadays, those tissues are also used for molecular characterization. Formalin is the most used fixative worldwide, and Bouin\u2019s solution in some worldwide institutions. Among molecular targets, micro RNAs (miRNAs), the single-stranded non-coding RNAs comprised of 18 to 24 nucleotides, have been demonstrated to be resistant to fixation and paraffin-embedding processes, with consequent possible application in clinical practice. In the present study, let-7e-5p, miR-423-3p, miR-92a-1-5p, miR-30d-5p, miR-155-5p, miR-200a-3p, and miR-429 were investigated in formalin and matched Bouin\u2019s solution-fixed tissues of high grade serous ovarian cancers by means of real-time and droplet digital PCR (ddPCR). Micro RNAs were detectable and analyzable in both formalin- and Bouin\u2019s-fixed specimens, but on average, higher Ct values and lower copies/\u3bcL were found in Bouin\u2019s-fixed samples. Data from formalin-fixed samples correlated significantly for most targets with Bouin\u2019s ones, except for let-7e-5p and miR-155-5p. This study shows that miRNAs are analyzable in both formalin- and Bouin\u2019s-fixed specimens, with the possibility, after proper data normalization, to compare miRNA-based data from formalin-fixed samples to those of Bouin\u2019s-fixed ones

The Bivariate Normal Copula

We collect well known and less known facts about the bivariate normal distribution and translate them into copula language. In addition, we prove a very general formula for the bivariate normal copula, we compute Gini's gamma, and we provide improved bounds and approximations on the diagonal.Comment: 24 page

Exploring wind direction and SO2 concentration by circular-linear density estimation

The study of environmental problems usually requires the description of variables with different nature and the assessment of relations between them. In this work, an algorithm for flexible estimation of the joint density for a circular-linear variable is proposed. The method is applied for exploring the relation between wind direction and SO2 concentration in a monitoring station close to a power plant located in Galicia (NW-Spain), in order to compare the effectiveness of precautionary measures for pollutants reduction in two different years.Comment: 17 pages, 7 figures, 2 table

Evaluation of a Set of miRNAs in 26 Cases of Fatal Traumatic Brain Injuries

In forensic medicine, identifying novel biomarkers for use as diagnostic tools to ascertain causes of death is challenging because of sample degradation. To that aim, a cohort (n = 26) of fatal traumatic brain injuries (TBIs) were tested for three candidate miRNAs (namely, miR-124-3p, miR-138-5p, and miR144-3p). For each case, three FFPE specimens (coup area (CA), contrecoup area (CCA), and the corpus callosum (CC)) were investigated, whereas the FFPE brain tissues of 45 subjects (deceased due to acute cardiovascular events) were used as controls. Relative quantification via the ∆∆Ct method returned significantly higher expression levels of the three candidate miRNAs (p < 0.01) in the TBI cases. No difference was detected in the expression levels of any miRNA investigated in the study among the CA, CCA, and CC. Furthermore, the analyzed miRNAs were unrelated to the TBI samples’ post-mortem intervals (PMIs). On the contrary, has-miR-124-3p ahashsa-miR-144-3p were significantly correlated (p < 0.01) with the agonal time in TBI deaths. Since the RNA was highly degraded in autoptic FFPE tissues, it was impossible to analyze the mRNA targets of the miRNAs investigated in the present study, highlighting the necessity of standardizing pre-analytical processes even for autopsy tissues

On the accuracy of PLIF measurements in slender plumes

The purpose of this article was to assess the measurement uncertainty of the planar laser-induced fluorescence (PLIF) method and, as much as possible, to devise corrections for predictable biases. More specifically, we considered the measurement of concentration maps in cross sections parallel to and normal to the axis of a slender plume containing Rhodamine 6G as a passive scalar tracer and transported by a turbulent shear flow. In addition to previously examined sources of error related to PLIF, we also investigated several unexplored ones. First, we demonstrated that errors would arise if the laser sheet thickness was comparable to or larger than the thickness of the instantaneous plume. We then investigated the effect of secondary fluorescence, which was attributed to absorption and re-emission of primary fluorescence by dye both within and outside the laser sheet. We found that, if uncorrected, this effect would contaminate the calibration as well as the instantaneous concentration measurements of the plume, and proposed methods for the correction of these errors and for identifying the instantaneous boundaries of the in-sheet dye regions

Subadventitial stenting around occluded stents: A bailout technique to recanalize in-stent chronic total occlusions

To evaluate the outcomes of subadventitial stenting (SS) around occluded stents for recanalizing in-stent chronic total occlusions (IS-CTOs).There is little evidence on the outcomes of SS for IS-CTO.We examined the outcomes of SS for IS-CTO PCI at 14 centers between July 2011 and June 2017, and compared them to historical controls recanalized using within-stent stenting (WSS). Target-vessel failure (TVF) on follow-up was the endpoint of this study, and was defined as a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization.During study period, 422 IS-CTO PCIs were performed, of which 32 (7.6%) were recanalized with SS, usually when conventional approaches failed. The most frequent CTO vessel was the right coronary artery (72%). Mean J-CTO score was 3.1 ± 0.9. SS was antegrade in 53%, and retrograde in 47%. Part of the occluded stent was crushed in 37%, while the whole stent was crushed in 63%. Intravascular imaging was used in 59%. One patient (3.1%) suffered tamponade. Angiographic follow-up was performed in 10/32 patients: stents were patent in six cases, one had mild neointimal hyperplasia, and three had severe restenosis at the SS site. Clinical follow-up was available for 29/32 patients for a mean of 388 ± 303 days. The 24-month incidence of TVF was 13.8%, which was similar to historical controls treated with WSS (19.5%, P = 0.49).SS is rarely performed, usually as last resort, to recanalize complex IS-CTOs. It is associated with favorable acute and mid-term outcomes, but given the small sample size of our study additional research is warranted