Machine Learning Identifies Digital Phenotyping Measures Most Relevant to Negative Symptoms in Psychotic Disorders: Implications for Clinical Trials.

BACKGROUND: Digital phenotyping has been proposed as a novel assessment tool for clinical trials targeting negative symptoms in psychotic disorders (PDs). However, it is unclear which digital phenotyping measurements are most appropriate for this purpose. AIMS: Machine learning was used to address this gap in the literature and determine whether: (1) diagnostic status could be classified from digital phenotyping measures relevant to negative symptoms and (2) the 5 negative symptom domains (anhedonia, avolition, asociality, alogia, and blunted affect) were differentially classified by active and passive digital phenotyping variables. METHODS: Participants included 52 outpatients with a PD and 55 healthy controls (CN) who completed 6 days of active (ecological momentary assessment surveys) and passive (geolocation, accelerometry) digital phenotyping data along with clinical ratings of negative symptoms. RESULTS: Machine learning algorithms classifying the presence of a PD diagnosis yielded 80% accuracy for cross-validation in H2O AutoML and 79% test accuracy in the Recursive Feature Elimination with Cross Validation feature selection model. Models classifying the presence vs absence of clinically significant elevations on each of the 5 negative symptom domains ranged in test accuracy from 73% to 91%. A few active and passive features were highly predictive of all 5 negative symptom domains; however, there were also unique predictors for each domain. CONCLUSIONS: These findings suggest that negative symptoms can be modeled from digital phenotyping data recorded in situ. Implications for selecting the most appropriate digital phenotyping variables for use as outcome measures in clinical trials targeting negative symptoms are discussed.

Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it?

Clinical and experimental advances related to the detection, magnitude and pathobiology of subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD), primarily observed in the presence of non-alcoholic steatohepatitis (NASH), prompt us to revisit current disease paradigms. Hepatic venous pressure gradient (HVPG) has been reported to underestimate portal pressure in NASH-related cirrhosis, while inaccuracy is more likely in non-cirrhotic livers, indicating a potential need for new and preferably non-invasive methods of measurement. Although clinically significant portal hypertension (HVPG ≥10 mmHg) retains its prognostic significance in NASH, subclinical portal hypertension (HVPG 6.0-9.5 mmHg) has been repeatedly detected in patients with NAFLD in the absence of cirrhosis or even significant fibrosis whereas the impact of these findings on disease outcomes remains unclear. Mechanocrine signalling pathways in various types of liver cell reveal a molecular basis for the adverse effects of subclinical portal hypertension and suggest a bidirectional relationship between portal pressure and fibrosis. These findings may guide efforts to improve risk assessment and identify novel therapeutic targets in NAFLD.

Simultaneous assessment of coronary stenosis relevance with automated computed tomography angiography and intravascular ultrasound analyses and fractional flow reserve.

OBJECTIVES: To assess the diagnostic performance of computed tomography angiography (CTA) and intravascular ultrasound (IVUS) derived minimum lumen areas (MLA) from the same lesions that correspond to an FFR ≤0.80. METHODS AND RESULTS: A total of 24 patients (33 arteries) were collected retrospectively according to the following inclusion criteria: presence of a CTA diagnostic followed by an IVUS and FFR percutaneous coronary procedures. CTA and IVUS lumen contours were automatically performed using previously validated methods.The correlation between CTA and IVUS for the MLA was r = 0.45. In terms of MLA, the mean difference between CTA and IVUS was 0.81 mm2. Of note, a much smaller CTA-derived MLA (2.10 mm2) was found to be related to significant FFR lesions compared to that of the MLA derived from IVUS (3.19 mm2). The area under the curve, accuracy, sensitivity and specificity for this CTA-derived MLA were 0.80, 0.76, 0.50 and 0.87, respectively, while these values for IVUS-derived MLA were 0.87, 0.85, 0.80 and 0.87. CONCLUSIONS: Computed tomography angiography and intravascular ultrasound-derived minimum lumen areas have moderate diagnostic efficiency, albeit slightly better for IVUS, in identifying hemodynamically severe coronary stenoses. The utility of MLA, automatically derived from either CTA or IVUS as an alternative to FFR to guide the decision to revascularize, should be tested clinically.

Nomograms of fetal cardiothoracic ratio from 17 to 37 weeks' gestation as assessed by three different measurement techniques and their correlation with gestational age.

OBJECTIVE: To create nomograms for fetal cardiothoracic (CT) ratio as assessed by three different 2-dimensional sonographic measurements, including CT diameter, circumference, and area ratios, in Thai fetuses with a gestational age (GA) of 17-37 weeks, and to evaluate both their correlation with GA or biparietal diameter (BPD) and variability among the three measurement methods. METHODS: Two-dimensional sonographic measurements of fetal CT ratio in 4-chamber view were assessed by three different measurement techniques. The 95% reference intervals and Z-scores of all measurement methods based on GA or BPD were constructed. Intraclass correlation coefficients (ICC) for the reproducibility of each technique were compared. RESULTS: A total of 511 uncomplicated singleton pregnancies were included. The fetal CT ratio values by all measurement techniques gradually and smoothly increased with increasing GA and BPD. The fetal CT circumference ratio showed the least correlation with both GA and BPD. The intraobserver and interobserver reliability coefficients of all techniques demonstrated almost excellent agreement (all ICCs at least 0.87). CONCLUSION: Reference intervals and Z-score reference ranges were developed using three different techniques for fetal CT ratio with a GA of 17-37 weeks. These nomograms are a simple and reliable screening tool for identifying abnormal fetal heart size.

Estimation of pulmonary artery pressure with transesophageal echocardiography: An observer-blinded test accuracy study.

ABSTRACT: With the declining use of the pulmonary artery catheter (PAC), transesophageal echocardiography (TEE) has become an appealing alternative to obtain pulmonary artery pressure non-invasively using the simplified Bernoulli equation. The validation of this method in the perioperative setting has been scarce with no clear recommendations about which view is the most accurate to estimate right ventricular systolic pressure (RVSP).Therefore, we performed a prospective, observer-blinded, diagnostic test accuracy study to assess the difference in systolic pulmonary artery pressure (sysPAP) measuring both, invasively sysPAP and estimated RVSP with TEE in 3 different views: the mid-esophageal (ME) 4Chamber, the ME right ventricular (RV) inflow-outflow and the ME modified bicaval view.To show a clinically significant difference of at least 10% in RVSP, we included 40 cardiac surgical patients divided into 3 subgroups: Patients with mild to moderate tricuspid regurgitation (TR) and mean PAP <25 mm Hg, patients with mild to moderate TR and mean PAP≥ 25 mm Hg, and patients with severe TR.For the whole cohort, bias of estimated RVSP compared to measured sysPAP was 5.27 mm Hg, precision was 7.96 mm Hg, limits of agreement were -10.66 to 21.19 mm Hg. The best agreement between the 2 methods was found in patients with severe TR and in the ME RV inflow-outflow and the modified bicaval view. Good Doppler signals were available in 35% and 46% in these views, and in 20% in the ME 4 chamber view.The estimation of the sysPAP by TEE cannot be considered reliable in the clinical perioperative setting. Only measurements that provide a full Doppler envelope show sufficient precision to provide accurate estimations.

Effect of physical therapy intervention on thickness and ratio of the sternocleidomastoid muscle and head rotation angle in infants with congenital muscular torticollis: A randomized clinical trial (CONSORT).

BACKGROUND: Early diagnosis as well as treatment is important in management of congenital muscular torticollis (CMT). The purpose of this study was to find an effective physical therapy modality to improve the sternocleidomastoid (SCM) muscle thickness, the ratio of the SCM muscle thickness on the affected side to that on the non-affected side (A/N ratio), and head rotation in infant under 3 months of age diagnosed with CMT. METHODS AND ANALYSIS: A single-blind, randomized clinical trial was conducted. Participants were assigned in one of the 3 study groups through randomization. The treatment was performed 3 times a week for 30 minutes until the head tilt was ≤5 degrees. Group 1 was treated by handling for active or active-assist movement, group 2 was treated with passive stretching, and group 3 was treated with thermotherapy. For general characteristics, a χ2 test and 1-way analysis of variance were used. Intragroup differences were analyzed using a paired t test, and intergroup differences were analyzed using an age-adjusted analysis of covariance. RESULTS: After the intervention, there was no significant difference between groups in terms of SCM thickness on the affected side and A/N ratio (P > .05). Degree of head rotation on the affected side showed significant differences between groups (P < .05), with Group 2 showing significantly better results than group 1 and group 3 (P < .05, both). CONCLUSION: Passive stretching treatment was more effective than other treatments of this study for improvement in degree of head rotation in CMT infants under 3 months of age. TRIAL REGISTRATION: The trial is registered at the Institutional Review Board of Sahmyook University (IRB number, 2-7001793-AB-N-012019103HR) and the Clinical Research Information Service (CRiS; registry number, KCT0004862).

Effects of dietary active soybean trypsin inhibitors on pancreatic weights, histology and expression of STAT3 and receptors for androgen and estrogen in different tissues of rats.

Our previous study showed that soy milks could contain high levels of active soybean trypsin inhibitors (SBTI) if they were not properly processed. This study investigated the effects of consuming active SBTI on pancreatic weights, histology, trypsinogen production and expression of STAT3, receptors for androgen (AR) and estrogen (ER) in pancreas, liver and uterus of rats. Weanling Sprague-Dawley rats were randomly divided into 3 groups (8 females and 8 males/group) and fed diets containing either 20% casein protein (Casein) or 20% soy protein (SP) in the presence of high (1.42 BAEE unit/µg, SP + SBTI) or low (0.2 BAEE unit/µg, SP-SBTI) levels of active SBTI for 8 weeks. Ingestion of SP + SBTI diet markedly increased pancreatic weights and trypsinogen content (p < 0.01), and caused acinar cell hypertrophy, and reduced pancreatic STAT3, p-STAT3, AR and ERß content, and increased uterine ERα and ERß compared to the Casein or SP-SBTI diets (p < 0.05). The two SP-containing diets lowered hepatic STAT3, p-STAT3, and pancreatic ERα, and increased hepatic ERα and ERß content in the female rats compared to the Casein diet (p < 0.05). This study demonstrated for the first time that consumption of high level of active SBTI not only increased pancreatic weights and acinar cell secretions, but also attenuated the expression of pancreatic STAT3, p-STAT3, AR, and ERß proteins in both sexes and increased uterine ERα and ERß content, and that dietary soy protein affected hepatic STAT3, p-STAT3, ERα and ERß in a gender-dependent manner.

Should singleton birth weight standards be applied to identify small-for-gestational age twins?: analysis of a retrospective cohort study.

BACKGROUND: Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. METHODS: This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. RESULTS: The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18-5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07-3.47). CONCLUSIONS: The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function.

OBJECTIVE: Cell diameter, area, and volume are established quantitative measures of adipocyte size. However, these different adipocyte sizing parameters have not yet been directly compared regarding their distributions. Therefore, the study aimed to investigate how these adipocyte size measures differ in their distribution and assessed their correlation with anthropometry and laboratory chemistry. In addition, we were interested to investigate the relationship between fat cell size and adipocyte mitochondrial respiratory chain capacity. METHODS: Subcutaneous and visceral histology-based adipocyte size estimates from 188 individuals were analyzed by applying a panel of parameters to describe the underlying cell population. Histology-based adipocyte diameter distributions were compared with adipocyte diameter distributions from collagenase digestion. Associations of mean adipocyte size with body mass index (BMI), glucose, HbA1C, blood lipids as well as mature adipocyte mitochondrial respiration were investigated. RESULTS: All adipocyte area estimates derived from adipose tissue histology were not normally distributed, but rather characterized by positive skewness. The shape of the size distribution depends on the adipocyte sizing parameter and on the method used to determine adipocyte size. Despite different distribution shapes histology-derived adipocyte area, diameter, volume, and surface area consistently showed positive correlations with BMI. Furthermore, associations between adipocyte sizing parameters and glucose, HbA1C, or HDL specifically in the visceral adipose depot were revealed. Increasing subcutaneous adipocyte diameter was negatively correlated with adipocyte mitochondrial respiration. CONCLUSIONS: Despite different underlying size distributions, the correlation with obesity-related traits was consistent across adipocyte sizing parameters. Decreased mitochondrial respiratory capacity with increasing subcutaneous adipocyte diameter could display a novel link between adipocyte hypertrophy and adipose tissue function.

Liver stiffness measured by magnetic resonance elastography in early recurrence of hepatocellular carcinoma after treatment: A protocol for systematic review and meta analysis.

BACKGROUND: With high diagnostic accuracy, magnetic resonance elastography (MRE) is a noninvasive tool and can be adopted to measure liver stiffness (LS). In this study, meta-analysis was carried out to further evaluate whether LS measured by MRE can predict early recurrence in patients with hepatocellular carcinoma (HCC). METHODS: PUBMED, EMBASE, Web of Science, China National Knowledge Infrastructure, and Cochrane Library database were searched for studies related to LS measured by MRE in the prediction of recurrence in patients with HCC. Survival outcome was estimated by hazard ratios and 95% confidence intervals. Meta-analysis was conducted with the Stata 16.0. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide evidence support for LS measured by MRE in predicting the recurrence of HCC. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/ OSF.IO / SURH3.

Usability of a Novel Instrument to Measure Damaged Peristomal Skin in Patients with an Ostomy.

OBJECTIVE: To evaluate the usability of a novel instrument (stoma ruler) to measure damaged peristomal skin in patients with an ostomy. METHODS: A wound ostomy and continence nurse used both the stoma ruler and a linear ruler to assess DET (discoloration, erosion, tissue overgrowth) scores and the height of protrusion above the skin of 10 patients with ileostomies and took photographs. The photographs were presented to five ostomy care nurses for reliability testing. The difference between the two methods was determined using paired Wilcoxon signed ranks test. PRIMARY OUTCOME MEASURE: Interrater reliability of the linear versus stoma ruler. RESULTS: The interrater reliabilities of the stoma ruler versus the linear ruler for the domain-area DET score were 0.95 (95% confidence interval, 0.89-0.99) and 0.68 (95% confidence interval, 0.42-0.89), respectively. Only nurse 5 reported a significant difference between the two rulers (z = -2.24, P = .03). CONCLUSIONS: In busy clinical settings, the stoma ruler is easy for ostomy care nurses to use to obtain accurate DET scores and the height of stoma protrusion above the skin. Observing the position of damaged skin using the clock marks on the stoma ruler enhance clinical description and reduce assessment variation among professionals.

First trimester fetal proportion volumetric measurements using a Virtual Reality approach.

OBJECTIVE: To establish feasibility and reproducibility of fetal proportion volumetric measurements, using three-dimensional (3D) ultrasound and a Virtual Reality (VR) system. METHODS: Within a population-based prospective birth cohort, 3D ultrasound datasets of 50 fetuses in the late first trimester were collected by three ultrasonographers in a single research center. V-scope software was used for volumetric measurements of total fetus, extremities, head-trunk, head, trunk, thorax, and abdomen. All measurements were performed independently by two researchers. Intraobserver and interobserver reproducibility were analyzed using Bland and Altman methods. RESULTS: Intraobserver and interobserver analyses of volumetric measurements of total fetus, head-trunk, head, trunk, thorax and abdomen showed intraclass correlation coefficients above 0.979, coefficients of variation below 7.51% and mean difference below 3.44%. The interobserver limits of agreement were within the ±10% range for volumetric measurements of total fetus, head-trunk, head and trunk. The interobserver limits of agreement for extremities, thorax and abdomen were -26.09% to 4.77%, -14.14% to 10.00% and -14.47% to 8.83%, respectively. CONCLUSION: First trimester fetal proportion volumetric measurements using 3D ultrasound and VR are feasible and reproducible, except volumetric measurements of the fetal extremities. These novel volumetric measurements may be used in future research to enable detailed studies on first trimester fetal development and growth.

Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study.

BACKGROUND: The availability of handheld, noninvasive sublingual video-microscopes allows for visualization of the microcirculation in critically ill patients. Recent studies demonstrate that reduced numbers of blood-perfused microvessels and increased penetration of erythrocytes into the endothelial glycocalyx are essential components of microvascular dysfunction. The aim of this study was to identify novel microvascular variables to determine the level of microvascular dysfunction in sepsis and its relationship with clinical variables. METHODS: This observational, prospective, cross-sectional study included 51 participants, of which 34 critically ill sepsis patients were recruited from intensive care units of a university hospital. Seventeen healthy volunteers served as controls. All participants underwent sublingual videomicroscopy by sidestream darkfield imaging. A new developed version of the Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell (RBC) velocity, RBC content, and blood flow in sublingual microvessels with diameters between 4 and 25 µm. RESULTS: A detailed analysis of adjacent diameter classes (1 µm each) of vessels between 4 and 25 µm revealed a severe reduction of vascular density in very small capillaries (5-7 µm), which correlated with markers of sepsis severity. Analysis of RBC velocity (VRBC) revealed a strong dependency between capillary and feed vessel VRBC in sepsis patients (R2 = 0.63, p < 0.0001) but not in healthy controls (R2 = 0.04, p = 0.43), indicating impaired capillary (de-)recruitment in sepsis. This finding enabled the calculation of capillary recruitment and dynamic capillary blood volume (CBVdynamic). Moreover, adjustment of PBR to feed vessel VRBC further improved discrimination between sepsis patients and controls by about 50%. By combining these dynamic microvascular and glycocalyx variables, we developed the microvascular health score (MVHSdynamic™), which decreased from 7.4 [4.6-8.7] in controls to 1.8 [1.4-2.7] in sepsis patients (p < 0.0001) and correlated with sepsis severity. CONCLUSION: We introduce new important diameter-specific quantification and differentiated analysis of RBC kinetics, a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect microvascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.

Agreement between continuous and intermittent pulmonary artery thermodilution for cardiac output measurement in perioperative and intensive care medicine: a systematic review and meta-analysis.

BACKGROUND: Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution are used in clinical practice it is important to know whether cardiac output measurements by the two methods are clinically interchangeable. METHODS: We performed a systematic review and meta-analysis of clinical studies comparing cardiac output measurements assessed using continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients. 54 studies with 1522 patients were included in the analysis. RESULTS: The heterogeneity across the studies was high. The overall random effects model-derived pooled estimate of the mean of the differences was 0.08 (95%-confidence interval 0.01 to 0.16) L/min with pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7 (95%-confidence interval 20.5 to 38.9)%. CONCLUSION: The heterogeneity across clinical studies comparing continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients is high. The overall trueness/accuracy of continuous pulmonary artery thermodilution in comparison with intermittent pulmonary artery thermodilution is good (indicated by a pooled mean of the differences < 0.1 L/min). Pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7% suggest that continuous pulmonary artery thermodilution barely passes interchangeability criteria with intermittent pulmonary artery thermodilution. PROSPERO registration number CRD42020159730.

RESPONSIVENESS OF UPPER LIMB SCALES AND TRUNK CONTROL FOR THE EVOLUTION OF PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY.

OBJECTIVE: To verify the interval of responsiveness to the scales Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limbs (PUL), and Jebsen Taylor Test (JTT) in patients with Duchenne Muscular Dystrophy (DMD). METHODS: We assessed patients with DMD aged 6 to 19 years old and with mini-mental (MMSE) score above 10 points. The assessments were performed individually, in a single session. The upper limb function was performed by PUL and JTT, and trunk control by SATCo-BR. Assessments were repeated six and 12 months after the initial assessment. The repeated-measures analysis of variance model and Bonferroni's multiple comparison method were employed as post hoc analysis; when the ANOVA assumptions were not met, the Friedman test was applied. RESULTS: The sample consisted of 28 patients evaluated in three moments (initial, and six and 12 months after the beginning). There was a time effect for the Upper Limb function performance in the total JTT, and for the subtests, except for subtests 1 and 6, which did not show a difference between the different moments. There was also a time effect for the score of total PUL, proximal PUL, intermediate PUL, and distal PUL. In the SATCo-BR, this effect was observed between the initial and 6 months, and between the initial and 12 months. CONCLUSIONS: The JTT, PUL, and SATCo-BR scales can detect changes over time, and they showed responsiveness to detect the evolution of the disease in the 6-month interval.

Do changes in pulse pressure variation and inferior vena cava distensibility during passive leg raising and tidal volume challenge detect preload responsiveness in case of low tidal volume ventilation?

BACKGROUND: In patients ventilated with tidal volume (Vt) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPVPLR) or in IVCDV (ΔIVCDVPLR) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDVVt) rather than changes in PPV (ΔPPVVt). METHODS: In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness. RESULTS: At baseline, IVCDV was not different between preload responders (n = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by - 38 ± 16% and - 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPVPLR, expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDVPLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPVVt, expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDVVt, but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3-18]%). CONCLUSIONS: During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable. TRIAL REGISTRATION: Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.

The origins of money: Calculation of similarity indexes demonstrates the earliest development of commodity money in prehistoric Central Europe.

The origins of money and the formulation of coherent weight and measurement systems are amongst the most significant prehistoric developments of the human intellect. We present a method for detecting perceptible standardization of weights and apply this to 5028 Early Bronze Age rings, ribs, and axe blades from Central Europe. We calculate the degree of uniformity on the basis of psychophysics, and quantify this using similarity indexes. The analysis shows that 70.3% of all rings could not be perceptibly distinguished from a ring weighing 195.5 grams, indicating their suitability as commodity money. Perceptive weight equivalence is demonstrated between rings, and a selection of ribs and axe blades. Co-occurrence of these objects evidences their interchangeability. We further suggest that producing copies of rings led to recognition of weight similarities and the independent emergence of a system of weighing in Central Europe at the end of the Early Bronze Age.

Responsiveness of upper limb scales and trunk control for the evolution of patients with duchenne muscular dystrophy / Responsividade de escalas de membro superior e controle de tronco na evolução de pacientes com distrofia muscular de duchenne

ABSTRACT Objective: To verify the interval of responsiveness to the scales Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limbs (PUL), and Jebsen Taylor Test (JTT) in patients with Duchenne Muscular Dystrophy (DMD). Methods: We assessed patients with DMD aged 6 to 19 years old and with mini-mental (MMSE) score above 10 points. The assessments were performed individually, in a single session. The upper limb function was performed by PUL and JTT, and trunk control by SATCo-BR. Assessments were repeated six and 12 months after the initial assessment. The repeated-measures analysis of variance model and Bonferroni's multiple comparison method were employed as post hoc analysis; when the ANOVA assumptions were not met, the Friedman test was applied. Results: The sample consisted of 28 patients evaluated in three moments (initial, and six and 12 months after the beginning). There was a time effect for the Upper Limb function performance in the total JTT, and for the subtests, except for subtests 1 and 6, which did not show a difference between the different moments. There was also a time effect for the score of total PUL, proximal PUL, intermediate PUL, and distal PUL. In the SATCo-BR, this effect was observed between the initial and 6 months, and between the initial and 12 months. Conclusions: The JTT, PUL, and SATCo-BR scales can detect changes over time, and they showed responsiveness to detect the evolution of the disease in the 6-month interval.

RESUMO Objetivo: Verificar o intervalo de tempo para a responsividade das escalas Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limb (PUL) e o Teste de Função Manual de Jebsen Taylor (TJT) em pacientes com distrofia muscular de Duchenne (DMD). Métodos: Foram avaliados pacientes com DMD nas idades entre 6 e 19 anos, e com escore do Mini Exame do Estado Mental (MEEM) a partir de 10 pontos. As avaliações foram realizadas individualmente, em uma única sessão: a função de membro superior (MS) ocorreu pela PUL e TJT; e da do controle de tronco, pela SATCo-BR. As avaliações foram repetidas após seis e 12 meses da avaliação inicial. Foi empregado o modelo de análise de variância com medidas repetidas e o método de comparações múltiplas de Bonferroni, como análise post hoc; quando os pressupostos da ANOVA não foram atendidos, foi aplicado o teste de Friedman. Resultados: A amostra foi composta por 28 pacientes avaliados em três momentos (inicial, após seis meses e após 12 meses). Houve efeito do tempo no desempenho da função Membro Superior no TJT total e nos subtestes, exceto nos subtestes 1 e 6, que não apresentaram diferença nas avaliações entre os diferentes momentos. Houve efeito do tempo para o escore da PUL total, PUL proximal, PUL intermediário e PUL distal. No SATCo-BR, esse efeito foi entre o inicial e após seis meses, e entre o inicial e após 12 meses. Conclusões: As escalas TJT, PUL e SATCo-BR são capazes de detectar alterações ao longo do tempo, e apresentam responsividade para detectar a evolução da doença em intervalo de 6 meses.

Performance of the cuff leak test in adults in predicting post-extubation airway complications: a systematic review and meta-analysis.

BACKGROUND: Clinical practice guidelines recommend performing a cuff leak test in mechanically ventilated adults who meet extubation criteria to screen those at high risk for post-extubation stridor. Previous systematic reviews demonstrated excellent specificity of the cuff leak test but disagreed with respect to sensitivity. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the cuff leak test for predicting post-extubation airway complications in intubated adult patients in critical care settings. METHODS: We searched Medline, EMBASE, Scopus, ISI Web of Science, the Cochrane Library for eligible studies from inception to March 16, 2020, without language restrictions. We included studies that examined the diagnostic accuracy of cuff leak test if post-extubation airway obstruction after extubation or reintubation was explicitly reported as the reference standard. Two authors in duplicate and independently assessed the risk of bias using the Quality Assessment for Diagnostic Accuracy Studies-2 tool. We pooled sensitivities and specificities using generalized linear mixed model approach to bivariate random-effects meta-analysis. Our primary outcomes were post-extubation airway obstruction and reintubation. RESULTS: We included 28 studies involving 4493 extubations. Three studies were at low risk for all QUADAS-2 risk of bias domains. The pooled sensitivity and specificity of cuff leak test for post-extubation airway obstruction were 0.62 (95% CI 0.49-0.73; I2 = 81.6%) and 0.87 (95% CI 0.82-0.90; I2 = 97.8%), respectively. The pooled sensitivity and specificity of the cuff leak test for reintubation were 0.66 (95% CI 0.46-0.81; I2 = 48.9%) and 0.88 (95% CI 0.83-0.92; I2 = 87.4%), respectively. Subgroup analyses suggested that the type of cuff leak test and length of intubation might be the cause of statistical heterogeneity of sensitivity and specificity, respectively, for post-extubation airway obstruction. CONCLUSIONS: The cuff leak test has excellent specificity but moderate sensitivity for post-extubation airway obstruction. The high specificity suggests that clinicians should consider intervening in patients with a positive test, but the low sensitivity suggests that patients still need to be closely monitored post-extubation.

A new metric for understanding hidden political influences from voting records.

Inspired by the increasing attention of the scientific community towards the understanding of human relationships and actions in social sciences, in this paper we address the problem of inferring from voting data the hidden influence on individuals from competing ideology groups. As a case study, we present an analysis of the closeness of members of the Italian Senate to political parties during the XVII Legislature. The proposed approach is aimed at automatic extraction of the relevant information by disentangling the actual influences from noise, via a two step procedure. First, a sparse principal component projection is performed on the standardized voting data. Then, the projected data is combined with a generative mixture model, and an information theoretic measure, which we refer to as Political Data-aNalytic Affinity (Political DNA), is finally derived. We show that the definition of this new affinity measure, together with suitable visualization tools for displaying the results of analysis, allows a better understanding and interpretability of the relationships among political groups.