Disentangling circular economy practices and firm's sustainability performance: A systematic literature review of past achievements and future promises.

This paper systematically and critically reviews the literature on the intersection of circular economy practices (CEPs) and sustainability performance (SP). We synthesize and analyze the extant literature to uncover the knowledge gaps, highlight the contradictory views, and provide a comprehensive overview of the field. Following a detailed database search, we selected 104 empirical studies published in peer-reviewed journals for analysis. Our review reports the publication trends, top publishing journal outlets, research methodologies, and empirical contexts. We outline the theoretical underpinnings, identify the diverse circular economy practices and the key factors that impact circular economy practices and sustainable performance. The review shows a propensity for most authors to reuse established theories or not use theory at all, revealing the need for theory development. Furthermore, our analysis revealed that R&D and innovation, digital technologies, organizational capabilities/resources, and stakeholder and institutional pressure substantially influence the CEPs - SP relationship. Through our detailed assessment of the existing literature, we identified and proposed several themes and avenues for future research.

The multidisciplinary Heart Team approach for patients with cardiovascular disease: a step towards personalized medicine.

AIMS: Despite general agreement on the benefits of the Heart Team approach for patients with cardiac diseases, few data are available on its real impact on the decision-making process. The aim of the study is to define the evolution over time of the level of agreement with the systematic discussion of patients in the Heart Team and to evaluate the adherence to the Heart Team recommendations and the impact of the Heart Team on the clinical outcome of the patients. METHODS: In 2015--2016, an experienced cardiac surgeon and a cardiologist independently reviewed clinical data of a series of 100 patients (Group 1, G1) and subsequently for each patient recommended treatment (surgical, percutaneous, hybrid or medical therapy) or further diagnostic investigations. The next day, each case was discussed by the Hospital Heart Team. The Heart Team recommendation, the subsequent treatment received by the patient and the in-hospital outcome were recorded. The same study procedure was repeated in 2017 in a second (G2) and in 2018 in a third (G3) group, both of them including 100 patients. RESULTS: Complete agreement in treatment selection by the cardiac surgeon, cardiologist and the Heart Team was observed in 43% of cases in G1 and in 70% and 68% in G2 and G3, respectively (G1 vs. G2: P  < 0.001, G1 vs. G3: P  = 0.01, G2 vs. G3: P  = 0.30). Agreement was less frequent in patients with a higher risk profile and in patients with aortic valve stenosis. The Heart Team decision was implemented in 95% of cases with a 30-day mortality of 0.67%. CONCLUSION: Agreement in treatment selection among the cardiac surgeon, cardiologist and Heart Team appears to be low in the initial experience. Subsequently, it seems to steadily increase over time up to a limit, when it reaches a plateau of stable results. Heart Team clinical cases discussion, based on both guidelines and multidisciplinary experience, represents a key step in defining the best patient treatment pathway, potentially improving the decision-making process and clinical results.

Microscale Neuronal Activity Collectively Drives Chaotic and Inflexible Dynamics at the Macroscale in Seizures.

Neuronal activity propagates through the network during seizures, engaging brain dynamics at multiple scales. Such propagating events can be described through the avalanches framework, which can relate spatiotemporal activity at the microscale with global network properties. Interestingly, propagating avalanches in healthy networks are indicative of critical dynamics, where the network is organized to a phase transition, which optimizes certain computational properties. Some have hypothesized that the pathologic brain dynamics of epileptic seizures are an emergent property of microscale neuronal networks collectively driving the brain away from criticality. Demonstrating this would provide a unifying mechanism linking microscale spatiotemporal activity with emergent brain dysfunction during seizures. Here, we investigated the effect of drug-induced seizures on critical avalanche dynamics, using in vivo whole-brain two-photon imaging of GCaMP6s larval zebrafish (males and females) at single neuron resolution. We demonstrate that single neuron activity across the whole brain exhibits a loss of critical statistics during seizures, suggesting that microscale activity collectively drives macroscale dynamics away from criticality. We also construct spiking network models at the scale of the larval zebrafish brain, to demonstrate that only densely connected networks can drive brain-wide seizure dynamics away from criticality. Importantly, such dense networks also disrupt the optimal computational capacities of critical networks, leading to chaotic dynamics, impaired network response properties and sticky states, thus helping to explain functional impairments during seizures. This study bridges the gap between microscale neuronal activity and emergent macroscale dynamics and cognitive dysfunction during seizures.SIGNIFICANCE STATEMENT Epileptic seizures are debilitating and impair normal brain function. It is unclear how the coordinated behavior of neurons collectively impairs brain function during seizures. To investigate this we perform fluorescence microscopy in larval zebrafish, which allows for the recording of whole-brain activity at single-neuron resolution. Using techniques from physics, we show that neuronal activity during seizures drives the brain away from criticality, a regime that enables both high and low activity states, into an inflexible regime that drives high activity states. Importantly, this change is caused by more connections in the network, which we show disrupts the ability of the brain to respond appropriately to its environment. Therefore, we identify key neuronal network mechanisms driving seizures and concurrent cognitive dysfunction.

Topographically Localized Modulation of Tectal Cell Spatial Tuning by Complex Natural Scenes.

The tuning properties of neurons in the visual system can be contextually modulated by the statistics of the area surrounding their receptive field (RF), particularly when the surround contains natural features. However, stimuli presented in specific egocentric locations may have greater behavioral relevance, raising the possibility that the extent of contextual modulation may vary with position in visual space. To explore this possibility, we utilized the small size and optical transparency of the larval zebrafish to describe the form and spatial arrangement of contextually modulated cells throughout an entire tectal hemisphere. We found that the spatial tuning of tectal neurons to a prey-like stimulus sharpens when the stimulus is presented against a background with the statistics of complex natural scenes, relative to a featureless background. These neurons are confined to a spatially restricted region of the tectum and have receptive fields centered within a region of visual space in which the presence of prey preferentially triggers hunting behavior. Our results suggest that contextual modulation of tectal neurons by complex backgrounds may facilitate prey-localization in cluttered visual environments.

Subclinical dysfunction of remote myocardium is related to high NT-proBNP and affects global contractility at follow-up, independently of infarct area.

Background: In ST-segment elevation myocardial infarction (STEMI), predictors of subclinical dysfunction of remote myocardium are unknown. We prospectively aimed at identifying clinical and biochemical correlates of remote subclinical dysfunction and its impact on left ventricular ejection fraction (LVEF). Methods: One-hundred thirty-three patients (63.9 ± 12.1 years, 68% male) with first successfully treated (54% anterior, 46% non-anterior, p = 0.19) STEMI underwent echocardiography at 5 ± 2 days after onset and at 8 ± 2-month follow-up, and were compared to 13 age and sex-matched (63.3 ± 11.4) healthy controls. All 16 left ventricular (LV) segments were grouped into ischemic, border, and remote myocardium: mean value of longitudinal strain (LS) within grouped segments were expressed as iLS, bLS, rLS, respectively. LV end-diastolic (EDV), end-systolic (ESV) volumes indexed for body surface area (EDVi, ESVi, respectively), LVEF and global LS (GLS) were determined. Creatinine, glomerular filtration rate, admission level of NT-pro-brain-natriuretic peptide (NT-proBNP) and troponin peaks were considered for the analysis. Results: At baseline, rLS (15.5 ± 4.4) was better than iLS (12.9 ± 4.8, p < 0.001), but lower than that in controls (19.1 ± 2.7, p < 0.001) and similar to bLS (15 ± 5.4, p = ns), and did not differ between patients with single or multivessel coronary artery disease (CAD). At multivariate regression analysis, only admission NT-proBNP levels but not peak Tn levels independently predicted rLS (ß = -0.58, p = 0.001), as well as iLS (ß = -0.52, p = 0.001). Both at baseline and at follow-up, rLS correlated to LVEF similarly to iLS and bLS (p < 0.001 for all). Median value of rLS at baseline was 15%: compared to patients with rLS ≥ 15% at baseline, patients with rLS < 15% showed lower LVEF (52.3 ± 9.4 vs. 58.6 ± 7.6, p < 0.001) and GLS (16.3 ± 3.9 vs. 19.9 ± 3.2), and higher EDVi (62.3 ± 19.9 vs. 54 ± 12, p = 0.009) and ESVi (30.6 ± 15.5 vs. 22.3 ± 7.6, p < 0.001) at follow-up. Conclusion: In optimally treated STEMI, dysfunction of remote myocardium assessed by LS: (1) is predicted by elevated NT-proBNP; (2) could be independent of CAD extent and infarct size; (3) is associated to worse LV morphological and functional indexes at follow-up.

Integrated OMICs unveil the bone-marrow microenvironment in human leukemia.

The bone-marrow (BM) niche is the spatial environment composed by a network of multiple stromal components regulating adult hematopoiesis. We use multi-omics and computational tools to analyze multiple BM environmental compartments and decipher their mutual interactions in the context of acute myeloid leukemia (AML) xenografts. Under homeostatic conditions, we find a considerable overlap between niche populations identified using current markers. Our analysis defines eight functional clusters of genes informing on the cellular identity and function of the different subpopulations and pointing at specific stromal interrelationships. We describe how these transcriptomic profiles change during human AML development and, by using a proximity-based molecular approach, we identify early disease onset deregulated genes in the mesenchymal compartment. Finally, we analyze the BM proteomic secretome in the presence of AML and integrate it with the transcriptome to predict signaling nodes involved in niche alteration in AML.

Colchicine in ischemic heart disease: the good, the bad and the ugly.

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

Human Papilloma Virus vaccine and prevention of head and neck cancer, what is the current evidence?

OBJECTIVES: Human Papilloma Virus is associated with the development of cancers in the head and neck region. We have witnessed, in the last decades, an increase in number of cases directly related to HPV infection, in particular in the Western Countries. Recently the FDA expanded the indications for Gardasil-9® to include the prevention of head and neck cancer. Objective of this paper is to review the evidence supporting its use. MATERIALS AND METHODS: Bibliographic review enquiring Medline, Web of Science and the Cochrane Library to assess the efficacy of vaccination against oncogenic HPV in the prevention of head and neck squamous cell carcinoma. RESULTS: Two prospective and 4 retrospective studies have evaluated vaccination in prevention of head and neck cancer, using persistent oral infection as surrogate of efficacy. All studies showed lower prevalence of oral infection up to 4 years following vaccination. Vaccine efficacy was estimated between 88 and 93.3%. Because of low vaccine coverage the estimated population-level effect against oral HPV16/18/6/11 infections was only 17.0%. CONCLUSIONS: Antibodies concentration in the oral fluid correlate with serum level, but the threshold to ensure protection is unknown. Duration of protection has not been established. HPV vaccination can provide protection from re-infection (at different mucosal sites) in previously exposed individuals, suggesting possible use of HPV vaccine later in life. Other studies should focus on confirming causal relationship between vaccination and prevention of persistent oral infection and investigate the duration of efficacy, which is crucial in its effectiveness against HNSCC.

A Multicellular Network Mechanism for Temperature-Robust Food Sensing.

Responsiveness to external cues is a hallmark of biological systems. In complex environments, it is crucial for organisms to remain responsive to specific inputs even as other internal or external factors fluctuate. Here, we show how the nematode Caenorhabditis elegans can discriminate between different food levels to modulate its lifespan despite temperature perturbations. This end-to-end robustness from environment to physiology is mediated by food-sensing neurons that communicate via transforming growth factor ß (TGF-ß) and serotonin signals to form a multicellular gene network. Specific regulations in this network change sign with temperature to maintain similar food responsiveness in the lifespan output. In contrast to robustness of stereotyped outputs, our findings uncover a more complex robustness process involving the higher order function of discrimination in food responsiveness. This process involves rewiring a multicellular network to compensate for temperature and provides a basis for understanding gene-environment interactions. Together, our findings unveil sensory computations that integrate environmental cues to govern physiology.

Cadherins regulate nuclear topography and function of developing ocular motor circuitry.

In the vertebrate central nervous system, groups of functionally related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.

Learning steers the ontogeny of an efficient hunting sequence in zebrafish larvae.

Goal-directed behaviors may be poorly coordinated in young animals but, with age and experience, behavior progressively adapts to efficiently exploit the animal's ecological niche. How experience impinges on the developing neural circuits of behavior is an open question. We have conducted a detailed study of the effects of experience on the ontogeny of hunting behavior in larval zebrafish. We report that larvae with prior experience of live prey consume considerably more prey than naive larvae. This is mainly due to increased capture success and a modest increase in hunt rate. We demonstrate that the initial turn to prey and the final capture manoeuvre of the hunting sequence were jointly modified by experience and that modification of these components predicted capture success. Our findings establish an ethologically relevant paradigm in zebrafish for studying how the brain is shaped by experience to drive the ontogeny of efficient behavior.

Bayesian inference of neuronal assemblies.

In many areas of the brain, both spontaneous and stimulus-evoked activity can manifest as synchronous activation of neuronal assemblies. The characterization of assembly structure and dynamics provides important insights into how brain computations are distributed across neural networks. The proliferation of experimental techniques for recording the activity of neuronal assemblies calls for a comprehensive statistical method to describe, analyze and characterize these high dimensional datasets. The performance of existing methods for defining assemblies is sensitive to noise and stochasticity in neuronal firing patterns and assembly heterogeneity. To address these problems, we introduce a generative hierarchical model of synchronous activity to describe the organization of neurons into assemblies. Unlike existing methods, our analysis provides a simultaneous estimation of assembly composition, dynamics and within-assembly statistical features, such as the levels of activity, noise and assembly synchrony. We have used our method to characterize population activity throughout the tectum of larval zebrafish, allowing us to make statistical inference on the spatiotemporal organization of tectal assemblies, their composition and the logic of their interactions. We have also applied our method to functional imaging and neuropixels recordings from the mouse, allowing us to relate the activity of identified assemblies to specific behaviours such as running or changes in pupil diameter.

A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture.

The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modeling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.

Thermodynamics of Majority-Logic Decoding in Information Erasure.

We investigate the performance of majority-logic decoding in both reversible and finite-time information erasure processes performed on macroscopic bits that contain N microscopic binary units. While we show that for reversible erasure protocols single-unit transformations are more efficient than majority-logic decoding, the latter is found to offer several benefits for finite-time erasure processes: Both the minimal erasure duration for a given erasure and the minimal erasure error for a given erasure duration are reduced, if compared to a single unit. Remarkably, the majority-logic decoding is also more efficient in both the small-erasure error and fast-erasure region. These benefits are also preserved under the optimal erasure protocol that minimizes the dissipated heat. Our work therefore shows that majority-logic decoding can lift the precision-speed-efficiency trade-off in information erasure processes.

Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.

The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX.

Quantification of Information Encoded by Gene Expression Levels During Lifespan Modulation Under Broad-range Dietary Restriction in C. elegans.

Sensory systems allow animals to detect, process, and respond to their environment. Food abundance is an environmental cue that has profound effects on animal physiology and behavior. Recently, we showed that modulation of longevity in the nematode Caenorhabditis elegans by food abundance is more complex than previously recognized. The responsiveness of the lifespan to changes in food level is determined by specific genes that act by controlling information processing within a neural circuit. Our framework combines genetic analysis, high-throughput quantitative imaging and information theory. Here, we describe how these techniques can be used to characterize any gene that has a physiological relevance to broad-range dietary restriction. Specifically, this workflow is designed to reveal how a gene of interest regulates lifespan under broad-range dietary restriction; then to establish how the expression of the gene varies with food level; and finally, to provide an unbiased quantification of the amount of information conveyed by gene expression about food abundance in the environment. When several genes are examined simultaneously under the context of a neural circuit, this workflow can uncover the coding strategy employed by the circuit.

Genetic control of encoding strategy in a food-sensing neural circuit.

Neuroendocrine circuits encode environmental information via changes in gene expression and other biochemical activities to regulate physiological responses. Previously, we showed that daf-7 TGFß and tph-1 tryptophan hydroxylase expression in specific neurons encode food abundance to modulate lifespan in Caenorhabditis elegans, and uncovered cross- and self-regulation among these genes (Entchev et al., 2015). Here, we now extend these findings by showing that these interactions between daf-7 and tph-1 regulate redundancy and synergy among neurons in food encoding through coordinated control of circuit-level signal and noise properties. Our analysis further shows that daf-7 and tph-1 contribute to most of the food-responsiveness in the modulation of lifespan. We applied a computational model to capture the general coding features of this system. This model agrees with our previous genetic analysis and highlights the consequences of redundancy and synergy during information transmission, suggesting a rationale for the regulation of these information processing features.

Minimally Invasive Versus Open Surgery For Acute Achilles Tendon Ruptures A Systematic Review And Meta-Analysis.

The minimally invasive surgery (MIS) approach has been popularised as an alternative to the standard open approach in acute Achilles tendon repair. Advocates of MIS suggest earlier functional recovery, due to reduced trauma to adjacent soft tissues. Critics, however, argue that due to inadequate surgical exposure, complications of such surgery are higher compared to an open technique. A systematic review and meta-analysis of randomised, prospective studies weas conducted to compare MIS and open surgery in acute Achilles tendon ruptures. Thirteen studies were included in the meta-analysis with a total of 854 patients. Although re-rupture rates were not significantly different between the groups (P = 0.43), there were significantly more complications in the open surgery group (P = <.00001). MIS in acute Achilles tendon ruptures result in similar re-rupture rates, sural nerve injury rates and return to sport time in comparison with open surgical method, but with significantly less post-operative complications.