Sparsest factor analysis for clustering variables: a matrix decomposition approach

We propose a new procedure for sparse factor analysis (FA) such that each variable loads only one common factor. Thus, the loading matrix has a single nonzero element in each row and zeros elsewhere. Such a loading matrix is the sparsest possible for certain number of variables and common factors. For this reason, the proposed method is named sparsest FA (SSFA). It may also be called FA-based variable clustering, since the variables loading the same common factor can be classified into a cluster. In SSFA, all model parts of FA (common factors, their correlations, loadings, unique factors, and unique variances) are treated as fixed unknown parameter matrices and their least squares function is minimized through specific data matrix decomposition. A useful feature of the algorithm is that the matrix of common factor scores is re-parameterized using QR decomposition in order to efficiently estimate factor correlations. A simulation study shows that the proposed procedure can exactly identify the true sparsest models. Real data examples demonstrate the usefulness of the variable clustering performed by SSFA

Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey

Background: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. / Methods: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. / Findings: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. / Interpretation: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. / Funding: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices

International multicenter observational study on assessment of ventilatory management during general anaesthesia for robotic surgery and its effects on postoperative pulmonary complication (AVATaR) : study protocol and statistical analysis plan

Introduction: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. Methods and analysis: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. Ethics and dissemination: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number: NCT02989415; Pre-results

A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species

Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per μL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.This research work has received funding from Junta de Andalucía, Consejería de Economía e Innovación (project number 2012-BIO1778), the Spanish Ministerio de Economía y Competitividad (Grants CTQ2012-34778, BIO2016-80519-R, FPI Grant BES-2013- 063020). This research was partially supported by the 7th European Community Framework Program (FP7-PEOPLE-2012-CIG-Project Number 322276)

Evaluation of Spatially Targeted Strategies to Control Non-Domiciliated Triatoma dimidiata Vector of Chagas Disease

Chagas disease is one of the most important parasitic diseases in Latin America. Since the 1980's, many national and international initiatives have contributed to eliminate vectors developing inside human domiciles. Today's challenge is to control vectors that are non-adapted to the human domicile, but still able to transmit the parasite through regular short stay in the houses. Here, we assess the potential of different control strategies applied in specific spatial patterns using a mathematical model that reproduces the dynamic of dispersion of such ‘non-domiciliated’ vectors within a village of the Yucatan Peninsula, Mexico. We show that no single strategy applied in the periphery of the village, where the insects are more abundant, provides satisfying protection to the whole village. However, combining the use of insect screens in houses at the periphery of the village (to simultaneously fight insects dispersing from the garden and the forest), and the cleaning of the peri-domicile areas of the centre of the village (where sylvatic insects are absent), would provide a cost-effective control. This type of spatially mixed strategy offers a promising way to reduce the cost associated with the repeated interventions required to control non-domiciliated vectors that permanently attempt to infest houses

The HIV-1 Nef protein binds argonaute-2 and functions as a viral suppressor of RNA interference

The HIV-1 accessory protein Nef is an important virulence factor. It associates with cellular membranes and modulates the endocytic machinery and signaling pathways. Nef also increases the proliferation of multivesicular bodies (MVBs), which are sites for virus assembly and budding in macrophages. The RNA interference (RNAi) pathway proteins Ago2 and GW182 localize to MVBs, suggesting these to be sites for assembly and turnover of the miRNA-induced silencing complex (miRISC). While RNAi affects HIV replication, it is not clear if the virus encodes a suppressor activity to overcome this innate host response. Here we show that Nef colocalizes with MVBs and binds Ago2 through two highly conserved Glycine-Tryptophan (GW) motifs, mutations in which abolish Nef binding to Ago2 and reduce virus yield and infectivity. Nef also inhibits the slicing activity of Ago2 and disturbs the sorting of GW182 into exosomes resulting in the suppression of miRNA-induced silencing. Thus, besides its other activities, the HIV-1 Nef protein is also proposed to function as a viral suppressor of RNAi (VSR)