Sensitivity Analysis of Whole-Room Indirect Calorimeters at the Steady-state Condition

Whole-Room Indirect Calorimeters (WRIC) are accurate tools to precisely measure energy metabolism in humans via calculation of oxygen consumption and carbon dioxide production. Yet, overall accuracy of metabolic measurements relies on the validity of the dynamic model for gas exchange inside the calorimeter volume in addition to experimental and environmental conditions that contribute to the uncertainty of WRIC outcome variables. The aim of this work is to formally study the sensitivity of a WRIC system operated in a push configuration at the steady-state condition to identify the optimal experimental conditions to obtain the best degree of accuracy for outcome metabolic measurements. The results of our sensitivity analysis are then validated with measurements obtained during propane combustion tests performed at the WRIC located at the University Hospital of Pisa. Our results demonstrate that achieving a fractional concentration of carbon dioxide inside the calorimeter >0.2% leads to relative uncertainty <5% for the outcome metabolic measurements when assuming an accuracy class of 1% for gas analyzer instruments

Static sensitivity of whole-room indirect calorimeters

Whole-room indirect calorimeters (WRIC) are accurate tools to precisely measure energy metabolism in humans via calculation of oxygen consumption and carbon dioxide production. Yet, overall accuracy of metabolic measurements relies on the validity of the theoretical model for gas exchange inside the WRIC volume in addition to experimental and environmental conditions that contribute to the uncertainty of WRIC outcome variables. The aim of this study was to quantitatively study the static sensitivity of a WRIC operated in a push configuration and located at the laboratories of the University Hospital of Pisa with the goal to identify the experimental conditions required to reach the best degree of accuracy for outcome metabolic measurements. Herein we demonstrate that achieving a fractional concentration of carbon dioxide inside the WRIC>0.2% at the steady state conditions allows to obtain a relative uncertainty <5% for the outcome metabolic measurement

Application of Pattern Recognition Techniques to the Classification of Full-Term and Preterm Infant Cry

Objectives: Scientific and clinical advances in perinatology and neonatology have enhanced the chances of survival of preterm and very low weight neonates. Infant cry analysis is a suitable noninvasive complementary tool to assess the neurologic state of infants particularly important in the case of preterm neonates. This article aims at exploiting differences between full-term and preterm infant cry with robust automatic acoustical analysis and data mining techniques. Study design: Twenty-two acoustical parameters are estimated in more than 3000 cry units from cry recordings of 28 full-term and 10 preterm newborns. Methods: Feature extraction is performed through the BioVoice dedicated software tool, developed at the Biomedical Engineering Lab, University of Firenze, Italy. Classification and pattern recognition is based on genetic algorithms for the selection of the best attributes. Training is performed comparing four classifiers: Logistic Curve, Multilayer Perceptron, Support Vector Machine, and Random Forest and three different testing options: full training set, 10-fold cross-validation, and 66% split. Results: Results show that the best feature set is made up by 10 parameters capable to assess differences between preterm and full-term newborns with about 87% of accuracy. Best results are obtained with the Random Forest method (receiver operating characteristic area, 0.94). Conclusions: These 10 cry features might convey important additional information to assist the clinical specialist in the diagnosis and follow-up of possible delays or disorders in the neurologic development due to premature birth in this extremely vulnerable population of patients. The proposed approach is a first step toward an automatic infant cry recognition system for fast and proper identification of risk in preterm babies

Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK)

: Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases

Primary Prophylaxis of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Revised Recommendations from a Consensus Process by Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

AVALIAÇÃO DE DOIS MÉTODOS DE TRITURAÇÃO FOLIAR DE Acianthera ciliata (Orchidaceae) PARA EXTRAÇÃO DE DNA

O estabelecimento de protocolo de extração de DNA de espécies vegetais é uma técnica empregada para a obtenção de um DNA puro e de qualidade. Diante disso, objetivou-se neste estudo padronizar um protocolo para a extração de DNA da espécie Acianthera ciliata, visando posteriores estudos de diversidade genética. Foram testados dois métodos de trituração do tecido foliar, sendo eles: Tampão STE e nitrogênio líquido. Para cada método de trituração foram testadas duas concentrações de β-mercaptoetanol (0% e 2%). Os dois métodos utilizados, foram eficientes na extração do DNA genômico de A. ciliata. As amostras extraídas com 0% de β-mercaptoetanol, para os dois métodos, STE e nitrogênio líquido, apresentaram menor quantidade de DNA quando comparado com as amostras extraídas com 2% de β-mercaptoetanol. Os dois primers testados amplificaram regiões do genoma de A. ciliata. Para a extração de DNA de A. ciliata indica-se a utilização de CTAB 5% no tampão de extração e β-mercaptoetanol a 2%. Os iniciadores ISSR foram eficientes na amplificação e são recomendados para estudos de diversidade genética de A. ciliata.Palavras-chave: diversidade genética; CTAB; marcadores moleculares; orquídeas. EVALUATION OF TWO MACERATION METHODS IN Acianthera ciliata (Orchidaceae) LEAVES FOR DNA EXTRACTION ABSTRACT: The establishment of DNA extraction protocol for plant species is a technique employed to obtain pure and good quality DNA. In this study, we standardized a protocol for the extraction of DNA of the species Acianthera ciliata, aiming studies of genetic diversity subsequently. Two maceration methods for foliar tissue were tested, and they were STE buffer and liquid nitrogen. Two concentrations of β-mercaptoethanol (0% and 2%) were tested for each method. The two methods used were efficient for genomic DNA extraction of A. ciliata. In both methods the samples extracted using 0% of β-mercaptoethanol, they presented lesser amount of DNA than the samples extracted using 2% of β-mercaptoethanol. The two tested primers amplified genomic regions of A. ciliata. For the DNA extraction of A. ciliata, we indicated the use of CTAB 5% in the extraction buffer as well as β-mercaptoethanol to 2%. The ISSR primers were efficient in amplification and thus they are indicated for studies of genetic diversity of A. ciliata.Keywords: genetic diversity; CTAB; molecular markers; orchids

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Greater male variability in daily energy expenditure develops through puberty

The authors also gratefully acknowledge funding from the Chinese Academy of Sciences (grant no. CAS153E11KYSB20190045) to J.R.S. and the US National Science Foundation (grant no. BCS-1824466) awarded to H.P. Acknowledgements Yvonne Schönbeck provided important information about morphometric measurements for Dutch children. A chat over dinner with Karsten Koehler, Eimear Dolan and Danny Longman brought up a number of thoughts that influenced this manuscript. The DLW database, which can be found at https://doublylabelled-waterdatabase.iaea.org/home, is hosted by the IAEA and generously supported by Taiyo Nippon Sanso and SERCON. We are grateful to the IAEA and these companies for their support and especially to Takashi Oono for his tremendous efforts at fundraising on our behalf.Peer reviewedPublisher PD