Failure to review STAT clinical laboratory requests and its economical impact

Background: Failure to follow-up laboratory test results has been described as one of the major processes contributing to unsafe patient care. Currently, most of the laboratories do not know with certainty not only their rate of missed (or unreviewed) requests but the economical cost and impact that this issue implies. The aim of our study was to measure that rate and calculate the resulting costs. Material and methods: In January 2015, we checked in our Laboratory Information Management System (LIMS) for every emergency request from 1st July 2011 to 30th June 2014, if they had been reviewed by any allowed user or not. 319,064 requests were ordered during that period of time. Results were expressed as “ordered requests”, “missed requests” and its percentage. Additionally, total cost of missed requests was calculated in euros (€). “Non-productive days” were theorised (as the days producing requests that were not reviewed) based on these results. Results: 7924 requests (2.5%) were never reviewed by clinicians. This represented a total cost of 203,039 € and 27 “non-productive” days in three years. Significant differences between inpatients, outpatients and emergency department as well as different emergencies units were found after application of statistical analysis. Conclusions: In terms of resources, never reviewed or missed requests appear to be a not negligible problem for the clinical laboratory management. Electronic result delivery, with electronic endorsement to indicate follow-up of requests along with better systems of electronic requesting should be investigated as a way of improving patient outcomes and save unnecessary expenses

Microarray analysis of autoimmune diseases by machine learning procedures

—Microarray-based global gene expression profiling, with the use of sophisticated statistical algorithms is providing new insights into the pathogenesis of autoimmune diseases. We have applied a novel statistical technique for gene selection based on machine learning approaches to analyze microarray expression data gathered from patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS), two autoimmune diseases of unknown genetic origin that share many common features. The methodology included a combination of three data discretization policies, a consensus gene selection method, and a multivariate correlation measurement. A set of 150 genes was found to discriminate SLE and PAPS patients from healthy individuals. Statistical validations demonstrate the relevance of this gene set from an univariate and multivariate perspective. Moreover, functional characterization of these genes identified an interferon-regulated gene signature, consistent with previous reports. It also revealed the existence of other regulatory pathways, including those regulated by PTEN, TNF, and BCL-2, which are altered in SLE and PAPS. Remarkably, a significant number of these genes carry E2F binding motifs in their promoters, projecting a role for E2F in the regulation of autoimmunity

Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation

OBJECTIVE: Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease. APPROACH AND RESULTS: We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions. CONCLUSIONS: Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation.This study was funded by the Spanish Ministry of Economy and Competiveness (MINECO; grants SAF2010-16044, SAF200911949), Instituto de Salud Carlos III (ISCIII; grants RD12/0042/0021, RD12/0042/0028, RD12/0042/0053), and the Dr Léon Dumont Prize 2010 by the Belgian Society of Cardiology (to Vicente Andrés). Patricia Fernández received salary support from ISCIII and Carlos Silvestre-Roig from Fundación Mario Losantos del Campo and Fundación Ferrer para la Investigación. Óscar M. Pello and Ricardo Rodríguez-Calvo hold a Juan de la Cierva contract from MINECO. Vanesa Esteban is an investigator of the Sara Borell program from ISCIII (CD06/00232). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by MINECO and Pro-CNIC Foundation.S

Renaturalización pasiva en la Cordillera Cantábrica: bases y retos científicos para una sostenibilidad socio-ecológica

La renaturalización pasiva, o recuperación de los ecosistemas tras el abandono del uso humano del territorio, representa una oportunidad para restaurar biodiversidad y servicios ecosistémicos en un contexto de crisis ambiental global. No obstante, también puede provocar declive de determinadas especies, cambios en los regímenes de perturbación o pérdidas de valores culturales. Esta revisión integra el conocimiento actual sobre patrones y procesos ecológicos de renaturalización pasiva en la Cordillera Cantábrica (NO España) para generar una primera base de evidencia sobre la que apoyar la gestión ambiental. Se observa un patrón de recuperación de bosques y matorrales en áreas anteriormente ocupadas por pastizales ganaderos y campos agrícolas, que implica cambios en la estructura del paisaje, la riqueza y la composición de las comunidades ecológicas, la acumulación de carbono en biomasa y suelos, y la provisión de diferentes servicios ecosistémicos. Los procesos que modulan la renaturalización son: 1) la dispersión de organismos, que condiciona la sucesión ecológica y la persistencia de especies a escala regional; 2) las dinámicas tróficas, cuyo funcionamiento depende de la presencia de grandes depredadores apicales y de la estructura del paisaje; y 3) los regímenes de perturbaciones ecológicas, actualmente dominados por la ganadería y los incendios antropogénicos. Por sus efectos ecológicos, la renaturalización pasiva representa una estrategia efectiva de restauración de ecosistemas y sus funciones clave en la Cordillera Cantábrica. Su aceptación social dependerá de la compatibilización de este proceso con el uso ganadero y ecoturístico del territorio, así como de la eficacia de las políticas conservacionistas, agrarias y forestales.Este trabajo recibe apoyo de los proyectos AYUD/2021/51261 (FICYT, Gobierno del Principado de Asturias, FEDER) y PID2019-107085RB-I00 (MCIN/AEI, FEDER). Rocío Rosa García proporcionó valiosa información sobre agroganadería y renaturalización. Mercedes Molina y dos revisores anónimos revisaron el manuscrito original

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Analysis of Attitude Jitter on the Performance of Feature Detection

This study explored a vision algorithm's performance during a shaker test to help reproduce the effects of vibration caused by the reaction wheels of a spacecraft. In this paper, we analyze the robustness of the feature detection technique by submitting the thermal and visible imaging cameras to sinusoidal vibrations as they simultaneously execute feature detection of the target

Failure to review STAT clinical laboratory requests and its economical impact

Background: Failure to follow-up laboratory test results has been described as one of the major processes contributing to unsafe patient care. Currently, most of the laboratories do not know with certainty not only their rate of missed (or unreviewed) requests but the economical cost and impact that this issue implies. The aim of our study was to measure that rate and calculate the resulting costs. Material and methods: In January 2015, we checked in our Laboratory Information Management System (LIMS) for every emergency request from 1st July 2011 to 30th June 2014, if they had been reviewed by any allowed user or not. 319,064 requests were ordered during that period of time. Results were expressed as “ordered requests”, “missed requests” and its percentage. Additionally, total cost of missed requests was calculated in euros (€). “Non-productive days” were theorised (as the days producing requests that were not reviewed) based on these results. Results: 7924 requests (2.5%) were never reviewed by clinicians. This represented a total cost of 203,039 € and 27 “non-productive” days in three years. Significant differences between inpatients, outpatients and emergency department as well as different emergencies units were found after application of statistical analysis. Conclusions: In terms of resources, never reviewed or missed requests appear to be a not negligible problem for the clinical laboratory management. Electronic result delivery, with electronic endorsement to indicate follow-up of requests along with better systems of electronic requesting should be investigated as a way of improving patient outcomes and save unnecessary expenses

Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation

Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment

Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes

Supplementary Video 1: CMAC-labeled Raji cells (blue) were attached to fibronectin-coated MatTek chamber slides and SEE-pulsed (30 min). Double synapse formation by one GFP-CD63-expressing Jurkat cell was time-lapse imaged (right side). The video shows MVB traffic to the synapse contact areas in this cell and not in Jurkat cells that do not form synapses (left). One representative example is shown of 11 synapses recorded.Supplementary Video 7: Synapse formed by a DsRed2-PKD1-expressing Jurkat T lymphocyte (red) with a SEE-loaded (1 μg/ml) , CMAC-labeled Raji B lymphocyte (blue). Both fluorescence channels were captured simultaneously in the video. The red channel was deconvoluted using Huygens Essential Software. DsRed2-PKD1 accumulation was observed at the synaptic contact after 30 min.Supplementary Video 8. WT mouse T lymphoblasts were challenged with SEB-pulsed (1 μg/ml), CMAC-labeled EL-4 cells (blue) at a 1:1 ratio and transmittance and blue channels were acquired. EL-4 cells were large and blue; T lymphoblasts were smaller and irregular. White arrows indicate synaptic contacts, red arrows indicate cells that show apoptotic blebbing. T, apoptosis of effector T lymphoblasts (AICD); EL4, death of EL-4 target cells (CTL).Multivesicular bodies (MVBs) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these ILV contain Fas ligand (FasL) and are secreted as 'lethal exosomes' following activation-induced fusion of the MVB with the plasma membrane. Diacylglycerol (DAG) and diacylglycerol kinase α (DGKα) regulate MVB maturation and polarized traffic, as well as subsequent secretion of pro-apoptotic exosomes, but the molecular basis underlying these phenomena remains unclear. Here we identify protein kinase D (PKD) family members as DAG effectors involved in MVB genesis and secretion. We show that the inducible secretion of exosomes is enhanced when a constitutively active PKD1 mutant is expressed in T lymphocytes, whereas exosome secretion is impaired in PKD2-deficient mouse T lymphoblasts and in PKD1/3-null B cells. Analysis of PKD2-deficient T lymphoblasts showed the presence of large, immature MVB-like vesicles and demonstrated defects in cytotoxic activity and in activation-induced cell death. Using pharmacological and genetic tools, we show that DGKα regulates PKD1/2 subcellular localization and activation. Our studies demonstrate that PKD1/2 is a key regulator of MVB maturation and exosome secretion, and constitutes a mediator of the DGKα effect on MVB secretory traffic.Mark Ware (Nanosight Ltd, UK) for his support in NANOSIGHT studies, and Catherine Mark for excellent editorial assistance. RA received a doctoral fellowship from the Spanish Ministerio de Ciencia y Tecnología. This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (MINECO) Plan Nacional de Investigación Científica (BFU2011-22849 to MI). IM is funded by MINECO grant BFU2013-47640-P.Peer Reviewe