Analyzing Nonequilibrium Quantum States through Snapshots with Artificial Neural Networks.

Current quantum simulation experiments are starting to explore nonequilibrium many-body dynamics in previously inaccessible regimes in terms of system sizes and timescales. Therefore, the question emerges as to which observables are best suited to study the dynamics in such quantum many-body systems. Using machine learning techniques, we investigate the dynamics and, in particular, the thermalization behavior of an interacting quantum system that undergoes a nonequilibrium phase transition from an ergodic to a many-body localized phase. We employ supervised and unsupervised training methods to distinguish nonequilibrium from equilibrium data, using the network performance as a probe for the thermalization behavior of the system. We test our methods with experimental snapshots of ultracold atoms taken with a quantum gas microscope. Our results provide a path to analyze highly entangled large-scale quantum states for system sizes where numerical calculations of conventional observables become challenging.

A tailored machine learning approach for mortality prediction in severe COVID-19 treated with glucocorticoids.

The impact of severe COVID-19 pneumonia on healthcare systems highlighted the need for accurate predictions to improve patient outcomes. Despite the established efficacy of glucocorticoids (GCs), variable patient responses are observed, and the existing clinical scores are limited in predicting non-responders. We propose a machine learning (ML) based approach to predict mortality in COVID-19 pneumonia treated with GCs.This is an ML-driven retrospective analysis involving 825 patients. We leveraged XGBoost to select the most appropriate features from the initial 52, including clinical and laboratory data. Six different ML techniques were compared. Shapley additive explanation (SHAP) values were used to describe the influence of each feature on classification. Internal validation was performed.Nine key predictors of death were identified: increasing C-reactive protein (CRP), decreasing arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2), age, coronary artery disease, invasive mechanical ventilation, acute renal failure, chronic heart failure, PaO2/FiO2 earliest value, and body mass index. Random forest achieved the highest test area under the receiver operating characteristic curve at 0.938 (95% CI 0.903-0.969). SHAP values highlighted age and PaO2/FiO2 improvement as the most influential features; the latter showed a higher impact than CRP reduction over time.The proposed ML algorithm effectively predicts the risk of hospital death in COVID-19 pneumonia patients undergoing GCs. This approach can be adapted to datasets measuring similar clinical variables..

Sufentanil Sublingual Tablet System: from rationale of use to clinical practice.

The control of post-operative pain in Italy and other western countries is still suboptimal. In recent years, the Sufentanil Sublingual Tablet System (SSTS; Zalviso; AcelRx Pharmaceuticals, Redwood City, CA, USA), which is designed for patient-controlled analgesia (PCA), has entered clinical practice. SSTS enables patients to manage moderate-to-severe acute pain during the first 72 postoperative hours directly in the hospital setting. However, the role of SSTS within the current framework of options for the management of post-operative pain needs to be better established. This paper presents the position on the use of SSTS of a multidisciplinary group of Italian Experts and provides protocols for the use of this device.

Intensive dietary intervention promoting the Mediterranean diet in people with high cardiometabolic risk: a non-randomized study.

AIMS: Mediterranean diet (MD) is acknowledged to exert a number of beneficial health effects. We assessed the efficacy and the durability of a 3-month intensive dietary intervention aimed at implementing the MD on body weight and cardiometabolic risk factors in subjects at high risk. METHODS: One hundred and sixteen subjects participated in the study (71 assigned to the intensive intervention and 45 to the conventional intervention). The intensive intervention consisted of 12 weekly group educational meetings and a free-of-charge supply of meals prepared according to the MD model. The conventional intervention consisted of an individual education session along with monthly reinforcements of nutritional messages by the general practitioner. All participants were followed up for 9 months. RESULTS: The two groups had similar pre-intervention characteristics. After the intervention, mean body weight decreased significantly in both groups (p < 0.001). However, the intervention group lost more weight (6.8 ± 4.0 vs. 0.7 ± 1.3, p < 0.0001) and showed a greater reduction in plasma glucose, triglycerides, blood pressure and an increase in HDL cholesterol than the control group (p < 0.01-p < 0.002). In the subgroup of participants with type 2 diabetes, there was a significant reduction in HbA1c level following the intensive (p < 0.0001) but not the conventional intervention. At follow-up, weight loss still persisted in the intervention group (p < 0.0001), while it was lost in the control group. Both interventions significantly reduced blood pressure in the long term (p < 0.001). A significant reduction in daily total energy intake was observed in both groups with a greater reduction in saturated fat and a higher increase in fibre intake in the intervention than in the control group (p < 0.009 and p < 0.001, respectively). CONCLUSIONS: A 3-month intensive dietary intervention inspired to the traditional MD produced greater and more durable weight loss and improvement in cardiometabolic risk profile than the conventional intervention.

Endothelial microparticles correlate with erectile dysfunction in diabetic men.

Cell-derived microparticles are supposed to be involved in endothelial dysfunction and atherogenesis. This study aimed to evaluate circulating microparticles in diabetic subjects with erectile dysfunction (ED) and their relation with endothelial dysfunction. Thirty diabetic men with ED and 20 age-matched control subjects without ED were assessed for circulating microparticles and endothelial dysfunction. Flow cytometry was used to assess microparticles by quantification of circulating endothelial (EMP, CD31(+)/CD42b(-)) and platelet (PMP, CD31(+)/CD42b(+)) microparticles in peripheral blood. Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. Compared with non-diabetic subjects, diabetic men presented significantly higher numbers of EMP (P=0.001), and reduced FMD (P=0.01), with a significant inverse correlation between the number of circulating EMP and the International Index of Erectile Function (IIEF) score (r=-0.457, P=0.01). Multivariate analysis correcting for age, anthropometric indices, glucose and lipid parameters, FMD and PMP identified EMP as the only independent predictor for IIEF score (P=0.03). EMP are elevated in impotent diabetic subjects and independently involved in the pathogenesis of ED.

Quality of vision: A consensus building initiative for a new ophthalmologic concept.

PURPOSE: Many studies have addressed the quantification of visual acuity, and the conventional method of measuring it has so far demonstrated serious limitations. Vision testing requires new methods that can more precisely express the quality of vision as perceived by the patient. METHODS: This study employed the Delphi method of consensus building. Concepts associated with quality of vision (QoV) were identified by a board of experts and proposed to participating specialists in two subsequent questionnaires. Upon receipt of the completed questionnaires, the replies were classified to determine the building blocks of a consensus. RESULTS: By analyzing the replies to the two questionnaires, the authors determined the key elements of QoV on which a consensus was found among the respondents. CONCLUSIONS: A consensus was reached on the opinion that the quantification of visual acuity by traditional means is inadequate for investigating QoV. Although visual acuity is still a basic element for testing, the experts believe that contrast sensitivity, reading speed, and microperimetry are additional parameters necessary for quantifying QoV. The use of a psychometric questionnaire on visual function could allow a better interpretation of visual impairment.

Localization, in human placenta, of the tightly bound form of DNA methylase in the higher order of chromatin organization.

In human placenta, the DNA of all subfractions of the third level of chromatin organization exhibits similar values of the methylcytosine-to-cytosine ratio. The tightly bound form of DNA methyltransferase is mostly recovered in the 'stripped loop' fraction, although, on the basis of the DNA content, the 'stripped loops' and the 'stripped matrix' appear to possess a similar amount of the enzyme. DNA methyltransferase activity is instead totally absent from the 'digested matrix', i.e., from the fraction remaining after digestion of the 'stripped matrix' with DNAase I. Upon addition of exogenous DNA methyltransferase, however, the DNA of this fraction, which is only 1% (in weight) of the total chromatin DNA and which has a length of approx. 9 kbp, can readily undergo methylation.

Histones and DNA methylation in mammalian chromatin. Differential inhibition by histone H1.

Histones (from calf thymus or from human placenta), if renatured in the presence of EDTA, caused a severe inhibition of in vitro methylation of double-stranded DNA (from Micrococcus luteus) by human placenta DNA methyltransferase. The absence of EDTA during the histone renaturation procedure abolished--at least in the 'physiological' range of the histones/DNA ratio--the inhibition. The H1 component was responsible for this inhibition, no effect being exerted by the other histones. H1 preparations were more effective if renatured in the presence of EDTA--90% inhibition being reached at a 0.3:1 (w/w) H1/DNA ratio. It seems likely that the requirement for the presence of EDTA during the renaturation process is correlated to its ability to induce a fairly stable ordered conformation of the histones, although this effect could also be shown with the 'inactive' H2a, H2b and H3 components, and was instead less evident with histone H1. The restriction to histone H1 of the ability to inhibit enzymic DNA methylation may account for the lower methylation levels present in the internucleosomal DNA of mammalian chromatin.

Substrate preferences of human placental DNA methyltransferase investigated with synthetic polydeoxynucleotides.

A DNA methyltransferase partly purified from human placenta has been tested on a variety of synthetic polydeoxynucleotides. The results showed that: the enzyme is most active as a 'maintenance' or 'hemi-' methylase but also has some de novo methylating activity; the presence or absence of A or T in the substrate strand has little influence on maintenance or de novo activity, while polymers containing C but not G in the same strand are poor de novo substrates and bind poorly to the enzyme; single-stranded polymers are about as good substrates as double-stranded ones, and the effects of nucleotide composition (particularly G and mC content) on enzyme activity with single strands are similar to those with double-stranded polymers; strands in which all the cytosines are methylated bind the enzyme well. A mechanism is suggested involving two different sites on the enzyme that recognize CG and mCG, and which rationalizes the activity of eukaryotic DNA methyltransferases towards single-stranded DNA.

Inactivation of de novo DNA methyltransferase activity by high concentrations of double-stranded DNA.

The activity of eukaryotic DNA methyltransferase diminishes with time when the enzyme is incubated with high concentrations (200-300 micrograms/ml) of unmethylated double-stranded Micrococcus luteus DNA. Under similar conditions, single-stranded DNA induces only a limited decrease of enzyme activity. The inactivation process is apparently due to a slowly progressive interaction of the enzyme with double-stranded DNA that is independent of the presence of S-adenosyl-L-methionine. The inhibited enzyme cannot be reactivated either by high salt dissociation of the DNA-enzyme complex or by extensive digestion of the DNA. Among synthetic polydeoxyribonucleotides both poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), but not poly(dI-dC).poly(dI-dC), cause inactivation of DNA methyltransferase. This inactivation process may be of interest in regulating the 'de novo' activity of the enzyme.

Me or my: two different patterns of pronoun case errors.

This paper investigates why some young children prefer to replace I with me (me-children), whereas others prefer to replace I with my (my-children). The data come from 12 children, observed monthly, from 1;0 to 3;0. It was found that the percentage of errors in which me replaced I (the me-error rate) was positively correlated with the correct production of me as an objective pronoun (the me-total). The me for I and my for I errors were antagonistic, with one of the patterns almost always dominating over the other, resulting in a clear individual difference between me-children and my-children. It was also found that the me-total during the period in which my for I replacements first emerged prefigured whether a child would become a me-child or a my-child.

The leading-edge: the significance of sentence disruptions in the development of grammar.

This research explored the relationship between sentence disruptions and the length and complexity of sentences spoken by children developing grammar. The study was cross-sectional in design and used samples of naturalistic, conversational interaction between 26 typically developing children (ages 2;6 to 4;0) and a primary caregiver. The active, declarative sentences produced by these children were coded for the presence of disruption, length in morphemes and words, and clausal complexity. The results showed that, for the majority of the children, disrupted sentences tended to be longer and more complex than fluent sentences. The magnitude of the differences in length and complexity was positively correlated with the children's grammatical development, as measured by the Index of Productive Syntax. It was also found that differences between the average complexity of disrupted versus fluent sentences increased with grammatical development even when sentence length was held constant. As grammatical development proceeded, disrupted sentences were more apt to be sentences on the "leading-edge" of the child's production capacity. Although these more advanced grammatical structures are part of the child's grammatical competence, the child cannot produce these sentences without an increased risk of processing difficulty. The results are congruent with proposals concerning the incremental and procedural nature of adult sentence production.

[Evaluation of heart rate changes in the aged. An ambulatory electrocardiography study. Arrhythmias in the aged]. / Valutazione delle alterazioni del ritmo cardiaco negli anziani. Studio mediante elettrocardiografia dinamica. Le aritmie negli anziani.

The Holter examinations of 111 subjects aged more than 65 who then underwent dynamic ecg were investigated in order to assess the clinical significance of cardiac arrhythmias in geriatric age. Group A was formed of 53 patients with no clinical signs of cardiovascular diseases. Thirty-two patients with clinical evidence of ischaemic cardiopathy made up Group B and 26 with arterial hypertension formed Group C. The Holter examinations were evaluated in accordance with current guidelines, considering the basic rhythm, heart rate, pulse formation and conduction disturbances and supraventricular and ventricular hyperkinetic arrhythmias. Sinus base rhythm was present in most cases whereas atrial fibrillation was noted in a similar percentage in the three groups, whether or not cardiovascular disease was present. Supraventricular and ventricular hyperkinetic arrhythmias were extremely common in the elderly and made no discrimination between patients with ischaemic cardiopathy or hypertension and the clinically healthy; for example, ventricular tachycardia was observed in 10.6% of Group A subjects, in 7.1% of Group B and 8.6% of Group C. To conclude, the clinical significance of heart rhythm changes in the elderly remains obscure because in most subjects they are not related to the presence of cardiovascular disease.

Pronoun case overextensions and paradigm building.

Pronoun case errors, or overextensions, like *me want it are characteristic of English child language. This paper explores a hypothesis that the morphological structure of a pronoun influences the pattern of these errors. The Language Acquisition Device (LAD) attempts to analyse English pronoun case forms into stems and affixes, but cannot because of their irregularity. Nevertheless the LAD extracts a phonetic core for each pronoun (e.g./m-/ for the 1st sg.,/h-/ for the 3rd masc. sg.). The phonetic core blocks the overextension of suppletive nominative forms like I and she. This hypothesis predicts strong differences in the frequency and types of errors between pronouns with suppletive nominatives and those without. Evidence for this hypothesis was found in a transcript database of twelve children, with data collected in one hour samples every month from 1;0 to 3;0. 20,908 pronouns were examined, 1347 of which were errors. Statistical analyses of these data provide support for this hypothesis.

Case and agreement in English language development.

This study examines the relationship between third person singular (3Psg) subject pronoun case and agreement, focusing on the hypothesis that these two grammatical subsystems develop together. This hypothesis is broken down into two separate, empirically testable hypotheses: (a) that correct subject case pronoun production and the production of agreement are correlated, and (b) that at the sentence level, correct case is dependent on the presence of agreement. Twenty-nine children between the ages of 2;6 and 4;0 were each audiotaped for approximately two hours playing and interacting with their primary caregivers. Transcribed production data showed that 3Psg masculine subject pronoun case was correlated with agreement marking, whereas 3Psg feminine subject pronoun case was not. This result suggests the influence of a retrieval factor, termed the double-cell effect, on the her for she pronoun case error. At the utterance level, pronoun case was independent of the presence of agreement. Overall, the study indicates that the relationship between case and agreement may be discernible as a general correlation, yet indiscernible at the level of sentence production.

Patterns of pronoun case error.

This paper addresses the question of whether the rate and patterns of pronoun case error are influenced by the composition of an individual pronoun's paradigm. Twenty-nine children, aged 2;6 to 4;0 were audiotaped for two 1-hour sessions, interacting with their primary caregivers engaged in free play, book reading and family album viewing. It was found that her was overextended for she at a significantly higher rate than him for he and them for they, providing evidence of a 'double-cell' effect that increases the incidence of error in the feminine pronoun. It was also found that the overextension of nominative forms (e.g. he for him), were antagonistic to the more frequently occurring type of overextension, objective for nominative (e.g. him for he). These findings indicate that the composition of a pronoun's paradigm influenced the patterns of pronoun case error observed.

Lexical assignability and perspective switch: the acquisition of verb subcategorization for aspectual inflections.

This paper explores how children learn the range of aspect inflections to which a verb is amenable. The data considered are from observations of three Japanese boys aged between 1:10 and 2:1. Analyses focus on the children's mastery of Aktionsart specific intersentential patterns. For example, in one pattern, a caregiver asks nani shiteiru? 'What is someone or something doing'. The conventional answer is with the continuative -te iru form of a verb that expresses an activity. Three conclusions are drawn. First, lexical assignment had begun before aspectual inflections were used to signal temporal perspective switch. Secondly, lexical assignment began with anchorpoints tying certain lexical contrasts to the Aktionsart of minimal sentences. Thirdly, overgeneralizations of aspect inflections are due to the difficulty of acquiring devices that signal temporal perspective switch.

The mosaic acquisition of grammatical relations.

The view that grammatical relations have substantial essence, designated as 'subject' or 'object' has difficulty in accounting for the variety of naturally acquirable grammatical relations. The acquisition of grammatical relations is examined from a theoretical framework, ROLE AND REFERENCE GRAMMAR, in which grammatical relations are decomposed into two separate types of structure: logical (semantic) structure and information (pragmatic) structure. The acquisition of grammatical relations from four languages is compared: (1) the definite accusative suffix and pragmatically motivated word order of Turkish; (2) Kaluli verb agreement, case and focus marking postpositions, and pragmatically motivated word order; (3) Hungarian definite and indefinite verb conjunction; and (4) Italian participial agreement and anaphoric, accusative case pronouns. Two conditions on structures are found to cause difficulty: the neutralization of a semantic or pragmatic distinction by interfering structures (e.g. Kaluli and Italian), and global case marking which forces the child to discover relevant semantic characteristics of both the actor and the undergoer (e.g. Hungarian and Kaluli). Structures that encode semantic or pragmatic distinctions independently are more easily acquired (e.g. Turkish). Piecing together discrete structures in a mosaic fashion, the child can acquire the great variety of grammatical relations that exist in human languages.