Asymptotic expansion of the minimum covariance determinant estimators

In arXiv:0907.0079 by Cator and Lopuhaa, an asymptotic expansion for the MCD estimators is established in a very general framework. This expansion requires the existence and non-singularity of the derivative in a first-order Taylor expansion. In this paper, we prove the existence of this derivative for multivariate distributions that have a density and provide an explicit expression. Moreover, under suitable symmetry conditions on the density, we show that this derivative is non-singular. These symmetry conditions include the elliptically contoured multivariate location-scatter model, in which case we show that the minimum covariance determinant (MCD) estimators of multivariate location and covariance are asymptotically equivalent to a sum of independent identically distributed vector and matrix valued random elements, respectively. This provides a proof of asymptotic normality and a precise description of the limiting covariance structure for the MCD estimators.Comment: 21 page

Affine equivariant rank-weighted L-estimation of multivariate location

In the multivariate one-sample location model, we propose a class of flexible robust, affine-equivariant L-estimators of location, for distributions invoking affine-invariance of Mahalanobis distances of individual observations. An involved iteration process for their computation is numerically illustrated.Comment: 16 pages, 4 figures, 6 table

Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue:proteome analysis of lung parenchyma, isolated endothelium, and thrombi

Aims: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. Methods: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. Results: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. Conclusions: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.</p

Preferences and beliefs of Dutch orthopaedic surgeons and patients reduce the implementation of "Choosing Wisely" recommendations in degenerative knee disease

Purpose: The purpose of this study was to assess which factors were associated with the implementation of “Choosing Wisely” recommendations to refrain from routine MRI and arthroscopy use in degenerative knee disease. Methods: Cross-sectional surveys were sent to 123 patients (response rate 95%) and 413 orthopaedic surgeons (response rate 62%) fulfilling the inclusion criteria. Univariate and multivariate logistic regression analyses were used to identify factors associated with implementation of “Choosing Wisely” recommendations. Results: Factors reducing implementation of the MRI recommendation among patients included explanation of added value by an orthopaedic surgeon [OR 0.18 (95% CI 0.07–0.47)] and patient preference for MRI [OR 0.27 (95% CI 0.08–0.92)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own MRI experience than existing evidence [OR 0.41 (95% CI 0.19–0.88)] and higher estimated patients’ knowledge to participate in shared decision-making [OR 0.38 (95% CI 0.17–0.88)]. Factors reducing implementation of the arthroscopy recommendation among patients were orthopaedic surgeons’ preferences for an arthroscopy [OR 0.03 (95% CI 0.00–0.22)] and positive experiences with arthroscopy of friends/family [OR 0.03 (95% CI 0.00–0.39)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own arthroscopy experience than existing evidence [OR 0.17 (95% CI 0.07–0.46)] and belief in the added value [OR 0.28 (95% CI 0.10–0.81)]. Conclusions: Implementation of “Choosing Wisely” recommendations in degenerative knee disease can be improved by strategies to change clinician beliefs about the added value of MRIs and arthroscopies, and by patient-directed strategies addressing patient preferences and underlying beliefs for added value of MRI and arthroscopies resulting from experiences of people in their environment. Level of evidence: IV

A robust measure of correlation between two genes on a microarray

<p>Abstract</p> <p>Background</p> <p>The underlying goal of microarray experiments is to identify gene expression patterns across different experimental conditions. Genes that are contained in a particular pathway or that respond similarly to experimental conditions could be co-expressed and show similar patterns of expression on a microarray. Using any of a variety of clustering methods or gene network analyses we can partition genes of interest into groups, clusters, or modules based on measures of similarity. Typically, Pearson correlation is used to measure distance (or similarity) before implementing a clustering algorithm. Pearson correlation is quite susceptible to outliers, however, an unfortunate characteristic when dealing with microarray data (well known to be typically quite noisy.)</p> <p>Results</p> <p>We propose a resistant similarity metric based on Tukey's biweight estimate of multivariate scale and location. The resistant metric is simply the correlation obtained from a resistant covariance matrix of scale. We give results which demonstrate that our correlation metric is much more resistant than the Pearson correlation while being more efficient than other nonparametric measures of correlation (e.g., Spearman correlation.) Additionally, our method gives a systematic gene flagging procedure which is useful when dealing with large amounts of noisy data.</p> <p>Conclusion</p> <p>When dealing with microarray data, which are known to be quite noisy, robust methods should be used. Specifically, robust distances, including the biweight correlation, should be used in clustering and gene network analysis.</p

COVID-19 in the Netherlands:lessons from a nationwide query of dutch autopsy, histology, and cytology pathological reports

Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide level. Pathology reports from all 43 pathology laboratories in the Netherlands stating “COVID,” “Corona,” and/or “SARS” were queried from the Dutch Nationwide Pathology Database (Palga). Consecutive reports of the included patients were also retrieved. Out of 5065 entries, a total of 1833 eligible COVID-19-related pathology reports between January 2020 and June 2021 were included in this collection of reports. Lung histopathology reports reflected differences in the severity of abnormalities (acute diffuse alveolar damage, alveolar histiocytes, and thrombi during the first three pandemic waves (Wuhan variant) versus the fourth wave (alpha variant)). Autopsy reports from 2020 state significantly shorter disease duration and younger age of death compared to autopsy reports from 2021. All reports together reflected a more granular pathology with comorbidities such as chronic histiocytic intervillositis, perniosis, and thrombi found in a variety of organs (lungs, kidneys, and small and large intestines). This nationwide overview of pathology reports provides data related to deaths as well as comorbidities in a clinical setting of COVID-19. Certain findings reported in SARS-CoV-infected lungs and placentas were also reported in post-COVID-19 tissue of the same kind. Consecutive reports after the earliest reports with COVID-19 allowed for follow-up reports. These follow-up reports can help with post-viral studies regarding long-term effects of COVID-19 as well as identifying the effects of different SARS-CoV-2 variants.</p

Consistency and asymptotic normality of least squares estimators in generalized STAR models

Abstract Space-time autoregressive (STAR) models, introduced b

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge

Background: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. Methods: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus ), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. Results: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P <0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). Conclusion: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhiniti