Dynamics and nonequilibrium states in the Hamiltonian mean-field model: A closer look

We critically revisit the evidence for the existence of quasistationary states in the globally coupled XY (or Hamiltonian mean-field) model. A slow-relaxation regime at long times is clearly revealed by numerical realizations of the model, but no traces of quasistationarity are found during the earlier stages of the evolution. We point out the nonergodic properties of this system in the short-time range, which makes a standard statistical description unsuitable. New aspects of the evolution during the nonergodic regime, and of the energy distribution function in the final approach to equilibrium, are disclosed

Environmental and economic assessment of sustainability in Mediterranean wheat production

ArticleThis study proposes the application of the Life Cycle Assessment (LCA) and economic evaluations conducted on different cereal production systems in semi-arid environments. Two different crop management systems of durum wheat were analysed by distinguishing Continuous Cropping (CC) and Crop Rotation (CR) with vetch, that are conducted through two different levels of crop intensification (in terms of tillage and fertilization strategies): Conventional (Conv) and Conservative (Cons). The resulting four scenarios were examined using LCA methodology to assess the environmental impacts, and the Production Cost (PC) analysis to estimate the economic results. Overall, the findings of this research provide an opportunity to identify sustainable crops management strategies

Applications of Information Theory to Analysis of Neural Data

Information theory is a practical and theoretical framework developed for the study of communication over noisy channels. Its probabilistic basis and capacity to relate statistical structure to function make it ideally suited for studying information flow in the nervous system. It has a number of useful properties: it is a general measure sensitive to any relationship, not only linear effects; it has meaningful units which in many cases allow direct comparison between different experiments; and it can be used to study how much information can be gained by observing neural responses in single trials, rather than in averages over multiple trials. A variety of information theoretic quantities are commonly used in neuroscience - (see entry "Definitions of Information-Theoretic Quantities"). In this entry we review some applications of information theory in neuroscience to study encoding of information in both single neurons and neuronal populations.Comment: 8 pages, 2 figure

Contrasting Effects of Lower Body Positive Pressure on Upper Airways Resistance and Partial Pressure of Carbon Dioxide in Men With Heart Failure and Obstructive or Central Sleep Apnea

ObjectivesThis study sought to test the effects of rostral fluid displacement from the legs on transpharyngeal resistance (Rph), minute volume of ventilation (Vmin), and partial pressure of carbon dioxide (PCO2) in men with heart failure (HF) and either obstructive (OSA) or central sleep apnea (CSA).BackgroundOvernight rostral fluid shift relates to severity of OSA and CSA in men with HF. Rostral fluid displacement may facilitate OSA if it shifts into the neck and increases Rph, because pharyngeal obstruction causes OSA. Rostral fluid displacement may also facilitate CSA if it shifts into the lungs and induces reflex augmentation of ventilation and reduces PCO2, because a decrease in PCO2 below the apnea threshold causes CSA.MethodsMen with HF were divided into those with mainly OSA (obstructive-dominant, n = 18) and those with mainly CSA (central-dominant, n = 10). While patients were supine, antishock trousers were deflated (control) or inflated for 15 min (lower body positive pressure [LBPP]) in random order.ResultsLBPP reduced leg fluid volume and increased neck circumference in both obstructive- and central-dominant groups. However, in contrast to the obstructive-dominant group in whom LBPP induced an increase in Rph, a decrease in Vmin, and an increase in PCO2, in the central-dominant group, LBPP induced a reduction in Rph, an increase in Vmin, and a reduction in PCO2.ConclusionsThese findings suggest mechanisms by which rostral fluid shift contributes to the pathogenesis of OSA and CSA in men with HF. Rostral fluid shift could facilitate OSA if it induces pharyngeal obstruction, but could also facilitate CSA if it augments ventilation and lowers PCO2

Cracking the code of oscillatory activity

Neural oscillations are ubiquitous measurements of cognitive processes and dynamic routing and gating of information. The fundamental and so far unresolved problem for neuroscience remains to understand how oscillatory activity in the brain codes information for human cognition. In a biologically relevant cognitive task, we instructed six human observers to categorize facial expressions of emotion while we measured the observers' EEG. We combined state-of-the-art stimulus control with statistical information theory analysis to quantify how the three parameters of oscillations (i.e., power, phase, and frequency) code the visual information relevant for behavior in a cognitive task. We make three points: First, we demonstrate that phase codes considerably more information (2.4 times) relating to the cognitive task than power. Second, we show that the conjunction of power and phase coding reflects detailed visual features relevant for behavioral response-that is, features of facial expressions predicted by behavior. Third, we demonstrate, in analogy to communication technology, that oscillatory frequencies in the brain multiplex the coding of visual features, increasing coding capacity. Together, our findings about the fundamental coding properties of neural oscillations will redirect the research agenda in neuroscience by establishing the differential role of frequency, phase, and amplitude in coding behaviorally relevant information in the brai

Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial

Background: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. Patients and methods: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting =6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. Results: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6–29.6] and 42.9% (95% CI 34.1–52.0), respectively. A reduction in the sum of the major diameters of BM =30% occurred in 42.9% (95% CI 34.1–52.0), including 49.3% (95% CI 36.9–61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3–5.6) months and 18.9 (95% CI 17.1–21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. Conclusion: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting

On Hilberg's Law and Its Links with Guiraud's Law

Hilberg (1990) supposed that finite-order excess entropy of a random human text is proportional to the square root of the text length. Assuming that Hilberg's hypothesis is true, we derive Guiraud's law, which states that the number of word types in a text is greater than proportional to the square root of the text length. Our derivation is based on some mathematical conjecture in coding theory and on several experiments suggesting that words can be defined approximately as the nonterminals of the shortest context-free grammar for the text. Such operational definition of words can be applied even to texts deprived of spaces, which do not allow for Mandelbrot's ``intermittent silence'' explanation of Zipf's and Guiraud's laws. In contrast to Mandelbrot's, our model assumes some probabilistic long-memory effects in human narration and might be capable of explaining Menzerath's law.Comment: To appear in Journal of Quantitative Linguistic

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

Process development and validation of expanded regulatory T cells for prospective applications: an example of manufacturing a personalized advanced therapy medicinal product

Background: A growing number of clinical trials have shown that regulatory T (Treg) cell transfer may have a favorable effect on the maintenance of self-tolerance and immune homeostasis in different conditions such as graft-versus-host disease (GvHD), solid organ transplantation, type 1 diabetes, and others. In this context, the availability of a robust manufacturing protocol that is able to produce a sufficient number of functional Treg cells represents a fundamental prerequisite for the success of a cell therapy clinical protocol. However, extended workflow guidelines for nonprofit manufacturers are currently lacking. Despite the fact that different successful manufacturing procedures and cell products with excellent safety profiles have been reported from early clinical trials, the selection and expansion protocols for Treg cells vary a lot. The objective of this study was to validate a Good Manufacturing Practice (GMP)-compliant protocol for the production of Treg cells that approaches the whole process with a risk-management methodology, from process design to completion of final product development. High emphasis was given to the description of the quality control (QC) methodologies used for the in-process and release tests (sterility, endotoxin test, mycoplasma, and immunophenotype). Results: The GMP-compliant protocol defined in this work allows at least 4.11 7 109 Treg cells to be obtained with an average purity of 95.75 \ub1 4.38% and can be used in different clinical settings to exploit Treg cell immunomodulatory function. Conclusions: These results could be of great use for facilities implementing GMP-compliant cell therapy protocols of these cells for different conditions aimed at restoring the Treg cell number and function, which may slow the progression of certain diseases