Large Pseudo-Counts and L2L_2-Norm Penalties Are Necessary for the Mean-Field Inference of Ising and Potts Models

Mean field (MF) approximation offers a simple, fast way to infer direct interactions between elements in a network of correlated variables, a common, computationally challenging problem with practical applications in fields ranging from physics and biology to the social sciences. However, MF methods achieve their best performance with strong regularization, well beyond Bayesian expectations, an empirical fact that is poorly understood. In this work, we study the influence of pseudo-count and $L_2$-norm regularization schemes on the quality of inferred Ising or Potts interaction networks from correlation data within the MF approximation. We argue, based on the analysis of small systems, that the optimal value of the regularization strength remains finite even if the sampling noise tends to zero, in order to correct for systematic biases introduced by the MF approximation. Our claim is corroborated by extensive numerical studies of diverse model systems and by the analytical study of the $m$-component spin model, for large but finite $m$. Additionally we find that pseudo-count regularization is robust against sampling noise, and often outperforms $L_2$-norm regularization, particularly when the underlying network of interactions is strongly heterogeneous. Much better performances are generally obtained for the Ising model than for the Potts model, for which only couplings incoming onto medium-frequency symbols are reliably inferred.Comment: 25 pages, 17 figure

Should we be concerned when COVID-19-positive patients take opioids to control their pain? Insights from a pharmacological point of view

Objective: The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches. Materials and methods: Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language. Results: Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters. Conclusions: Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder

“Salus Populi Suprema Lex”: Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis

FRET Dyes Significantly Affect SAXS Intensities of Proteins

Structural analyses in biophysics aim at revealing a relationship between a molecule's dynamic structure and its physiological function. Förster resonance energy transfer (FRET) and small‐angle X‐ray scattering (SAXS) are complementary experimental approaches to this. Their concomitant application in combined studies has recently opened a lively debate on how to interpret FRET measurements in the light of SAXS data with the popular example of the radius of gyration, commonly derived from both FRET and SAXS. There still is a lack of understanding in how to mutually relate and interpret quantities equally obtained from FRET or SAXS, and to what extent FRET dyes affect SAXS intensities in combined applications. In the present work, we examine the interplay of FRET and SAXS from a computational simulation perspective. Molecular simulations are a valuable complement to experimental approaches and supply instructive information on dynamics. As FRET depends not only on the mutual separation but also on the relative orientations, the dynamics, and therefore also the shapes of the dyes, we utilize a novel method for simulating FRET‐dye‐labeled proteins to investigate these aspects in atomic detail. We perform structure‐based simulations of four different proteins with and without dyes in both folded and unfolded conformations. In‐silico derived radii of gyration are different with and without dyes and depend on the chosen dye pair. The dyes apparently influence the dynamics of unfolded systems. We find that FRET dyes attached to a protein have a significant impact on theoretical SAXS intensities calculated from simulated structures, especially for small proteins. Radii of gyration from FRET and SAXS deviate systematically, which points to further underlying mechanisms beyond prevalent explanation approaches

Incidence of pneumomediastinum in COVID-19: A single-center comparison between 1st and 2nd wave

In this study, we compared the incidence of pneumomediastinum in coronavirus disease (COVID-19) patients during the ascending phases of the 1st and 2nd epidemic waves. Crude incidence was higher during the 2nd wave at a quasi-significant level (0.68/1000 vs. 2.05/1000 patient-days, p = 0.05). When restricting the analysis to patients who developed pneumomediastinum during noninvasive ventilation, the difference became clearly significant (0.17/1000 vs 1.36/1000 patient-days, p = 0.039). At logistic regression, predisposing factors (p = 0.031), and COVID-19 radiological severity (p = 0.019) were independently associated with pneumomediastinum. Mortality in patients with pneumomediastinum was 87.5%. However, pneumomediastinum seemed to be related to a generally worse disease presentation in hospitalized patients during the 2nd wave, rather than to a separate pattern of disease. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved

Growth of β intermetallic in an Al-Cu-Si alloy during directional solidification via machine learned 4D quantification

Fe contamination is a serious composition barrier for Al recycling. In Fe-containing Al-Si-Cu alloy, a brittle and plate-shaped β phase forms, degrading the mechanical properties. 4D (3D plus time) synchrotron X-ray tomography was used to observe the directional solidification of Fe-containing Al-Si-Cu alloy. The quantification of the coupled growth of the primary and β phase (Al5FeSi) via machine learning and particle tracking, demonstrates that the final size of the β intermetallics was strongly influenced by the solute segregation and space available for growth. The temperature gradient direction controlled the β orientation. The work can be used to validate predictive models

The combined use of VIGl@ct (R) (bioMerieux) and fluorescent amplified length fragment polymorphisms in the investigation of potential outbreaks

Even with good surveillance programmes, hospital-acquired infections (HAls) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAls, based on the use of a real-time epidemiological information system called VIGI@ct (R) (bioMerieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total, of 306 suspicious HAls. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the tatter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESPL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct (R) and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gramnegative bacteria and yeasts. (C) 2007 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved

Therapeutic strategies in severe neuropsychiatric systemic lupus erythematosus: experience from a tertiary referral centre.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) still remains empirical and based on clinical experience due to the lack of randomized controlled trials. Objective: to report the experience accumulated in a single tertiary referral centre about treatment of severe cases of NPSLE patients and to discuss therapeutic strategies on the background of EULAR recommendations. Methods: retrospective analysis of all consecutive cases of severe NPSLE treated in our centre since 1990 to 2010, satisfying the 1999 ACR criteria. Results: among 633 SLE patients who consecutively attended our centre, 231 (36%) displayed at least one neuropsychiatric (NP) manifestation for a total of 408 events attributable to SLE. Thirty-one patients (4.8%), 27 females and 4 males, experienced 35 major NP events requiring immunosuppressive therapy (including 3 relapses and 1 new event). An aggressive immunosuppressive strategy was applied to those patients with an immune mediated inflammatory NP event and to those patients with an increased disease activity as judged by ECLAM and SLEDAI scores. Overall at the end of the therapy 74% of the patients reached clinical remission or significant improvement of their symptoms measured by mean SLEDAI (from 10.09±1.09 to 2.04±0.52, P<0.0001) and ECLAM (from 4±0.34 to 1.38±0.37, P<0.001) scores. Conclusions: the prevalence of NP involvement, described in our case series, is similar to those reported in literature as well as the treatment strategies applied. Nowadays, it is not possible to establish a standardized approach for each single NPSLE manifestation, and different therapeutic strategies must be tailored taking into account the most probable pathogenic mechanism involved, the general disease activity background, the co-morbidities, the type and the stage of the systemic involvement

Task-relevant grasp selection: A joint solution to planning grasps and manipulative motion trajectories

This paper addresses the problem of jointly planning both grasps and subsequent manipulative actions. Previously, these two problems have typically been studied in isolation, however joint reasoning is essential to enable robots to complete real manipulative tasks. In this paper, the two problems are addressed jointly and a solution that takes both into consideration is proposed. To do so, a manipulation capability index is defined, which is a function of both the task execution waypoints and the object grasping contact points. We build on recent state-of-the-art grasp-learning methods, to show how this index can be combined with a likelihood function computed by a probabilistic model of grasp selection, enabling the planning of grasps which have a high likelihood of being stable, but which also maximise the robot's capability to deliver a desired post-grasp task trajectory. We also show how this paradigm can be extended, from a single arm and hand, to enable efficient grasping and manipulation with a bi-manual robot. We demonstrate the effectiveness of the approach using experiments on a simulated as well as a real robot

Turbulent characteristics in the intensity fluctuations of a solar quiescent prominence observed by the \textit{Hinode} Solar Optical Telescope

We focus on Hinode Solar Optical Telescope (SOT) calcium II H-line observations of a solar quiescent prominence (QP) that exhibits highly variable dynamics suggestive of turbulence. These images capture a sufficient range of scales spatially ($\sim$0.1-100 arc seconds) and temporally ($\sim$16.8 s - 4.5 hrs) to allow the application of statistical methods used to quantify finite range fluid turbulence. We present the first such application of these techniques to the spatial intensity field of a long lived solar prominence. Fully evolved inertial range turbulence in an infinite medium exhibits multifractal \emph{scale invariance} in the statistics of its fluctuations, seen as power law power spectra and as scaling of the higher order moments (structure functions) of fluctuations which have non-Gaussian statistics; fluctuations $\delta I(r,L)=I(r+L)-I(r)$ on length scale $L$ along a given direction in observed spatial field $I$ have moments that scale as $<\delta I(r,L)^p>\sim L^{\zeta(p)}$. For turbulence in a system that is of finite size, or that is not fully developed, one anticipates a generalized scale invariance or extended self-similarity (ESS) $\sim G(L)^{\zeta(p)}$. For these QP intensity measurements we find scaling in the power spectra and ESS. We find that the fluctuation statistics are non-Gaussian and we use ESS to obtain ratios of the scaling exponents $\zeta(p)$: these are consistent with a multifractal field and show distinct values for directions longitudinal and transverse to the bulk (driving) flow. Thus, the intensity fluctuations of the QP exhibit statistical properties consistent with an underling turbulent flow