Forecasting seasonal influenza fusing digital indicators and a mechanistic disease model

The availability of novel digital data streams that can be used as proxy for monitoring infectious disease incidence is ushering in a new era for real-time forecast approaches to disease spreading. Here, we propose the first seasonal influenza forecast framework based on a stochastic, spatially structured mechanistic model (individual level microsimulation) initialized with geo-localized microblogging data. The framework provides for more than 600 census areas in the United States, Italy and Spain, the initial conditions for a stochastic epidemic computational model that generates an ensemble of forecasts for the main indicators of the epidemic season: peak time and intensity. We evaluate the forecasts accuracy and reliability by comparing the results from our framework with the data from the official influenza surveillance systems in the US, Italy and Spain in the seasons 2014/15 and 2015/16. In all countries studied, the proposed framework provides reliable results with leads of up to 6 weeks that became more stable and accurate with progression of the season. The results for the United States have been generated in real-time in the context of the Centers for Disease Control and Prevention “Forecasting the Influenza Season Challenge". A characteristic feature of the mechanistic modeling approach is in the explicit estimate of key epidemiological parameters relevant for public health decision-making that cannot be achieved with statistical models not considering the disease dynamic. Furthermore, the presented framework allows the fusion of multiple data streams in the initialization stage and can be enriched with census, weather and socioeconomic data

Molecular and Physiological Effects of Browning Agents on White Adipocytes from Bone Marrow Mesenchymal Stromal Cells

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the ‘browning of WAT’. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity

Social data mining and seasonal influenza forecasts: The FluOutlook platform

FluOutlook is an online platform where multiple data sources are integrated to initialize and train a portfolio of epidemic models for influenza forecast. During the 2014/15 season, the system has been used to provide real-time forecasts for 7 countries in North America and Europe

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as "browning" or "beiging". These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs

Combining participatory influenza surveillance with modeling and forecasting

Background: Influenza outbreaks affect millions of people every year and its surveillance is usually carried out in developed countries through a network of sentinel doctors who report the weekly number of Influenza-like Illness cases observed among the visited patients. Monitoring and forecasting the evolution of these outbreaks supports decision makers in designing effective interventions and allocating resources to mitigate their impact. Objectives: Describe the existing participatory surveillance approaches that have been used for modeling and forecasting of the seasonal influenza epidemic, and how they can help strengthen real-time epidemic science and provide a more rigorous understanding of epidemic conditions. Methods: We describe three different participatory surveillance systems, WISDM (Widely Internet Sourced Distributed Monitoring), InfluenzaNet and Flu Near You (FNY), and show how modeling and simulation can be or has been combined with participatory disease surveillance to: i) measure the non-response bias in a participatory surveillance sample using WISDM; and ii) nowcast and forecast influenza activity in different parts of the world (using InfluenzaNet and Flu Near You). Results: WISDM based results measure the participatory and sample bias for three epidemic metrics i.e. attack rate, peak infection rate, and time-to-peak, and find the participatory bias to be the largest component of the total bias. InfluenzaNet platform shows that digital participatory surveillance data combined with a realistic data-driven epidemiological model can provide both short-term and long-term forecasts of epidemic intensities; and the ground truth data lie within the 95 percent confidence intervals for most weeks. The statistical accuracy of the ensemble forecasts increase as the season progresses. The Flu Near You platform shows that participatory surveillance data provide accurate short-term flu activity forecasts and influenza activity predictions. The correlation of the HealthMap Flu Trends estimates with the observed CDC ILI rates is 0.99 for 2013-2015. Additional data sources lead to an error reduction of about 40% when compared to the estimates of the model that only incorporates CDC historical information. Conclusions: While the advantages of participatory surveillance, compared to traditional surveillance, include its timeliness, lower costs, and broader reach, it is limited by a lack of control over the characteristics of the population sample. Modeling and simulation can help overcome this limitation as well as provide real-time and long term forecasting of Influenza activity in data poor parts of the world

New System Delivering Microwaves Energy for Inducing Subcutaneous Fat Reduction: In - Vivo Histological and Ultrastructural Evidence

BACKGROUND: Recently, it has been developed a new technology for the reduction of subcutaneous adipose tissue through a non-invasive treatment by microwaves. The main objective of the present study is to demonstrate the feasibility of utilising a non-invasive, localised microwaves (MW) device to induce thermal modifications into subcutaneous adipose tissue only by a controlled electromagnetic field that heats up fat preferentially. This device is provided with a special handpiece appropriately cooled, directly contacting the cutaneous surface of the body, which provides a calibrated energy transfer by microwaves. AIM: In this paper, microscopic and ultrastructural modifications of subcutaneous adipose tissue induced by microwaves irradiation are evaluated. METHODS: Our experimental plan was designed for collecting biopsy samples, for each skin region treated with a single irradiation session, 1) before treatment (control), 2) immediately after treatment, 3) after 6 hrs, 4) after 1 month, 5) after 2 months. Bioptic samples from each step were processed for light microscopy and transmission electron microscopy. At the same time, each region where biopsies were collected was subjected to ultrasound examination. Recorded images permitted to evaluate the thickness of different layers as epidermis, dermis, hypodermis, connective fasciae, until to muscle layer, and related modifications induced by treatment. RESULTS: In every biopsy collected at different time-steps, epidermis and superficial dermis appeared not modified compared to control. Differently, already in the short-term biopsies, in the deep dermis and superficial hypodermis, fibrillar connective tissue appeared modified, showing reduction and fragmentation of interlobular collagen septa. The most important adipose tissue modifications were detectable following 1 month from treatment, with a significant reduction of subcutaneous fat, participating both the lysis of many adipocytes and the related phagocytic action of monocytes/macrophages on residuals of compromised structures of adipocytes. In the samples collected two months following treatment, the remnants of adipose tissue appeared normal, and macrophages were completely absent. CONCLUSIONS: Ultrasound, microscopic and ultrastructural evidence are supporting significant effectiveness of the new device treatment in the reduction of subcutaneous fat. In this paper, the possible mechanisms involved in the activation of the monocytes/macrophages system responsible for the removal of adipocytes residuals have also been discussed

Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients.</p> <p>Case presentation</p> <p>We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation.</p> <p>Conclusion</p> <p>This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.</p

Perturbations in cosmologies with a scalar field and a perfect fluid

We study the properties of cosmological density perturbations in a multi-component system consisting of a scalar field and a perfect fluid. We discuss the number of degrees of freedom completely describing the system, introduce a full set of dynamical gauge-invariant equations in terms of the curvature and entropy perturbations, and display an efficient formulation of these equations as a first-order system linked by a fairly sparse matrix. Our formalism includes spatial gradients, extending previous formulations restricted to the large-scale limit, and fully accounts for the evolution of an isocurvature mode intrinsic to the scalar field. We then address the issue of the adiabatic condition, in particular demonstrating its preservation on large scales. Finally, we apply our formalism to the quintessence scenario and clearly underline the importance of initial conditions when considering late-time perturbations. In particular, we show that entropy perturbations can still be present when the quintessence field energy density becomes non-negligible.Comment: RevTex4, 9 pages, 3 figures. Significant additions on the quintessence scenario (new appendix and additional numerical example). Conclusions unchanged, but more robus

Health technology assessment of intensive care ventilators for pediatric patients

This paper is aimed at addressing all the critical aspects linked to the implementation of intensive care ventilators in a pediatric setting, highlighting the most relevant technical features and describing the methodology to conduct health technology assessment (HTA) for supporting the decision-making process. Four ventilator models were included in the assessment process. A decision-making support tool (DoHTA method) was applied. Twenty-eight Key Performance Indicators (KPIs) were identified, defining the safety, clinical effectiveness, organizational, technical, and economic aspects. The Performance scores of each ventilator have been measured with respect to KPIs integrated with the total cost of ownership analysis, leading to a final rank of the four possible technological solutions. The final technologies’ performance scores reflected a deliver valued, contextualized, and shared outputs, detecting the most performant technological solution for the specific hospital context. HTA results had informed and supported the pediatric hospital decision-making process. This study, critically identifying the pros and cons of innovative features of ventilators and the evaluation criteria and aspects to be taken into account during HTA, can be considered as a valuable proof of evidence as well as a reliable and transferable method for conducting decision-making processes in a hospital context

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200&nbsp;mg three times daily or placebo for up to 21&nbsp;days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51