Evaluation of the Spatiotemporal Epidemiological Modeler (STEM) during the recent COVID-19 pandemic.

In early December 2019, some people in China were diagnosed with an unknown pneumonia in Wuhan, in the Hubei province. The responsible of the outbreak was identified in a novel human-infecting coronavirus which differs both from severe acute respiratory syndrome coronavirus and from Middle East respiratory syndrome coronavirus. The new coronavirus, officially named severe acute respiratory syndrome coronavirus 2 by the International Committee on Taxonomy of Viruses, has spread worldwide within few weeks. Only two vaccines have been approved by regulatory agencies and some others are under development. Moreover, effective treatments have not been yet identified or developed even if some potential molecules are under investigation. In a pandemic outbreak, when treatments are not available, the only method that contribute to reduce the virus spreading is the adoption of social distancing measures, like quarantine and isolation. With the intention of better managing emergencies like this, which are a great public health threat, it is important to dispose of predictive epidemiological tools that can help to understand both the virus spreading in terms of people infected, hospitalized, dead and recovered and the effectiveness of containment measures.

Data driven theory for knowledge discovery in the exact sciences with applications to thermonuclear fusion.

In recent years, the techniques of the exact sciences have been applied to the analysis of increasingly complex and non-linear systems. The related uncertainties and the large amounts of data available have progressively shown the limits of the traditional hypothesis driven methods, based on first principle theories. Therefore, a new approach of data driven theory formulation has been developed. It is based on the manipulation of symbols with genetic computing and it is meant to complement traditional procedures, by exploring large datasets to find the most suitable mathematical models to interpret them. The paper reports on the vast amounts of numerical tests that have shown the potential of the new techniques to provide very useful insights in various studies, ranging from the formulation of scaling laws to the original identification of the most appropriate dimensionless variables to investigate a given system. The application to some of the most complex experiments in physics, in particular thermonuclear plasmas, has proved the capability of the methodology to address real problems, even highly nonlinear and practically important ones such as catastrophic instabilities. The proposed tools are therefore being increasingly used in various fields of science and they constitute a very good set of techniques to bridge the gap between experiments, traditional data analysis and theory formulation.

First Prototype of the Infectious Diseases Seeker (IDS) Software for Prompt Identification of Infectious Diseases.

The rapid detection of ongoing outbreak - and the identification of causative pathogen - is pivotal for the early recognition of public health threats. The emergence and re-emergence of infectious diseases are linked to several determinants, both human factors - such as population density, travel, and trade - and ecological factors - like climate change and agricultural practices. Several technologies are available for the rapid molecular identification of pathogens [e.g. real-time polymerase chain reaction (PCR)], and together with on line monitoring tools of infectious disease activity and behaviour, they contribute to the surveillance system for infectious diseases. Web-based surveillance tools, infectious diseases modelling and epidemic intelligence methods represent crucial components for timely outbreak detection and rapid risk assessment. The study aims to integrate the current prevention and control system with a prediction tool for infectious diseases, based on regression analysis, to support decision makers, health care workers, and first responders to quickly and properly recognise an outbreak. This study has the intention to develop an infectious disease regressive prediction tool working with an off-line database built with specific epidemiological parameters of a set of infectious diseases of high consequences. The tool has been developed as a first prototype of a software solution called Infectious Diseases Seeker (IDS) and it had been established in two main steps, the database building stage and the software implementation stage (MATLAB® environment). The IDS has been tested with the epidemiological data of three outbreaks occurred recently: severe acute respiratory syndrome epidemic in China (2002-2003), plague outbreak in Madagascar (2017) and the Ebola virus disease outbreak in the Democratic Republic of Congo (2018). The outcomes are promising and they reveal that the software has been able to recognize and characterize these outbreaks. The future perspective about this software regards the developing of that tool as a useful and user-friendly predictive tool appropriate for first responders, health care workers, and public health decision makers to help them in predicting, assessing and contrasting outbreaks.

A novel integrated approach for the hazardous radioactive dust source terms estimation in future nuclear fusion power plants.

An open issue still under investigation by several international entities working on the safety and security field for the foreseen nuclear fusion reactors is the estimation of source terms that are a hazard for the operators and public, and for the machine itself in terms of efficiency and integrity in case of severe accident scenarios. Source term estimation is a crucial key safety issue to be addressed in the future reactors safety assessments, and the estimates available at the time are not sufficiently satisfactory. The lack of neutronic data along with the insufficiently accurate methodologies used until now, calls for an integrated methodology for source term estimation that can provide predictions with an adequate accuracy. This work proposes a complete methodology to estimate dust source terms starting from a broad information gathering. The wide number of parameters that can influence dust source term production is reduced with statistical tools using a combination of screening, sensitivity analysis, and uncertainty analysis. Finally, a preliminary and simplified methodology for dust source term production prediction for future devices is presented.

Testing the accuracy ratio of the Spatio-Temporal Epidemiological Modeler (STEM) through Ebola haemorrhagic fever outbreaks.

Mathematical modelling is an important tool for understanding the dynamics of the spread of infectious diseases, which could be the result of a natural outbreak or of the intentional release of pathogenic biological agents. Decision makers and policymakers responsible for strategies to contain disease, prevent epidemics and fight possible bioterrorism attacks, need accurate computational tools, based on mathematical modelling, for preventing or even managing these complex situations. In this article, we tested the validity, and demonstrate the reliability, of an open-source software, the Spatio-Temporal Epidemiological Modeler (STEM), designed to help scientists and public health officials to evaluate and create models of emerging infectious diseases, analysing three real cases of Ebola haemorrhagic fever (EHF) outbreaks: Uganda (2000), Gabon (2001) and Guinea (2014). We discuss the cases analysed through the simulation results obtained with STEM in order to demonstrate the capability of this software in helping decision makers plan interventions in case of biological emergencies.

Image computing techniques to extrapolate data for dust tracking in case of an experimental accident simulation in a nuclear fusion plant.

In this paper, a preliminary shadowgraph-based analysis of dust particles re-suspension due to loss of vacuum accident (LOVA) in ITER-like nuclear fusion reactors has been presented. Dust particles are produced through different mechanisms in nuclear fusion devices, one of the main issues is that dust particles are capable of being re-suspended in case of events such as LOVA. Shadowgraph is based on an expanded collimated beam of light emitted by a laser or a lamp that emits light transversely compared to the flow field direction. In the STARDUST facility, the dust moves in the flow, and it causes variations of refractive index that can be detected by using a CCD camera. The STARDUST fast camera setup allows to detect and to track dust particles moving in the vessel and then to obtain information about the velocity field of dust mobilized. In particular, the acquired images are processed such that per each frame the moving dust particles are detected by applying a background subtraction technique based on the mixture of Gaussian algorithm. The obtained foreground masks are eventually filtered with morphological operations. Finally, a multi-object tracking algorithm is used to track the detected particles along the experiment. For each particle, a Kalman filter-based tracker is applied; the particles dynamic is described by taking into account position, velocity, and acceleration as state variable. The results demonstrate that it is possible to obtain dust particles' velocity field during LOVA by automatically processing the data obtained with the shadowgraph approach.

Contact X-ray microscopy of living cells by using LiF crystal as imaging detector.

In this paper, the use of lithium fluoride (LiF) as imaging radiation detector to analyse living cells by single-shot soft X-ray contact microscopy is presented. High resolved X-ray images on LiF of cyanobacterium Leptolyngbya VRUC135, two unicellular microalgae of the genus Chlamydomonas and mouse macrophage cells (line RAW 264.7) have been obtained utilizing X-ray radiation in the water window energy range from a laser plasma source. The used method is based on loading of the samples, the cell suspension, in a special holder where they are in close contact with a LiF crystal solid-state X-ray imaging detector. After exposure and sample removal, the images stored in LiF by the soft X-ray contact microscopy technique are read by an optical microscope in fluorescence mode. The clear image of the mucilaginous sheath the structure of the filamentous Leptolyngbya and the visible nucleolus in the macrophage cells image, are noteworthiness results. The peculiarities of the used X-ray radiation and of the LiF imaging detector allow obtaining images in absorption contrast revealing the internal structures of the investigated samples at high spatial resolution. Moreover, the wide dynamic range of the LiF imaging detector contributes to obtain high-quality images. In particular, we demonstrate that this peculiar characteristic of LiF detector allows enhancing the contrast and reveal details even when they were obscured by a nonuniform stray light.

UMEL: a new regression tool to identify measurement peaks in LIDAR/DIAL systems for environmental physics applications.

Recently, surveying large areas in an automatic way, for early detection of both harmful chemical agents and forest fires, has become a strategic objective of defence and public health organisations. The Lidar and Dial techniques are widely recognized as a cost-effective alternative to monitor large portions of the atmosphere. To maximize the effectiveness of the measurements and to guarantee reliable monitoring of large areas, new data analysis techniques are required. In this paper, an original tool, the Universal Multi Event Locator, is applied to the problem of automatically identifying the time location of peaks in Lidar and Dial measurements for environmental physics applications. This analysis technique improves various aspects of the measurements, ranging from the resilience to drift in the laser sources to the increase of the system sensitivity. The method is also fully general, purely software, and can therefore be applied to a large variety of problems without any additional cost. The potential of the proposed technique is exemplified with the help of data of various instruments acquired during several experimental campaigns in the field.

Improved equilibrium reconstructions by advanced statistical weighting of the internal magnetic measurements.

In a Tokamak the configuration of the magnetic fields remains the key element to improve performance and to maximise the scientific exploitation of the device. On the other hand, the quality of the reconstructed fields depends crucially on the measurements available. Traditionally in the least square minimisation phase of the algorithms, used to obtain the magnetic field topology, all the diagnostics are given the same weights, a part from a corrective factor taking into account the error bars. This assumption unduly penalises complex diagnostics, such as polarimetry, which have a limited number of highly significant measurements. A completely new method to choose the weights, to be given to the internal measurements of the magnetic fields for improved equilibrium reconstructions, is presented in this paper. The approach is based on various statistical indicators applied to the residuals, the difference between the actual measurements and their estimates from the reconstructed equilibrium. The potential of the method is exemplified using the measurements of the Faraday rotation derived from JET polarimeter. The results indicate quite clearly that the weights have to be determined carefully, since the inappropriate choice can have significant repercussions on the quality of the magnetic reconstruction both in the edge and in the core. These results confirm the limitations of the assumption that all the diagnostics have to be given the same weight, irrespective of the number of measurements they provide and the region of the plasma they probe.

Influence of plasma diagnostics and constraints on the quality of equilibrium reconstructions on Joint European Torus.

One of the main approaches to thermonuclear fusion relies on confining high temperature plasmas with properly shaped magnetic fields. The determination of the magnetic topology is, therefore, essential for controlling the experiments and for achieving the required performance. In Tokamaks, the reconstruction of the fields is typically formulated as a free boundary equilibrium problem, described by the Grad-Shafranov equation in toroidal geometry and axisymmetric configurations. Unfortunately, this results in mathematically very ill posed problems and, therefore, the quality of the equilibrium reconstructions depends sensitively on the measurements used as inputs and on the imposed constraints. In this paper, it is shown how the different diagnostics (Magnetics Measurements, Polarimetry and Motional Stark Effect), together with the edge current density and plasma pressure constraints, can have a significant impact on the quality of the equilibrium on JET. Results show that both the Polarimetry and Motional Stark Effect internal diagnostics are crucial in order to obtain reasonable safety factor profiles. The impact of the edge current density constraint is significant when the plasma is in the H-mode of confinement. In this plasma scenario the strike point positions and the plasma last closed flux surface can change even by centimetres, depending on the edge constraints, with a significant impact on the remapping of the equilibrium-dependent diagnostics and of pedestal physics studies. On the other hand and quite counter intuitively, the pressure constraint can severely affect the quality of the magnetic reconstructions in the core. These trends have been verified with several JET discharges and consistent results have been found. An interpretation of these results, as interplay between degrees of freedom and available measurements, is provided. The systematic analysis described in the paper emphasizes the importance of having sufficient diagnostic inputs and of properly validating the results of the codes with independent measurements.

Mutual interaction of Faraday rotation and Cotton­Mouton phase shift in JET polarimetric measurements.

The paper presents a study of Faraday rotation (FR) angle and Cotton­Mouton (CM) phase shift measurements to determine their mutual interaction and the validity of the linear models presently used in equilibrium codes. Comparison between time traces of measurements and model calculations leads to the result that only an exact numerical solution of Stokes equations can reproduce in all the experimental data. As a consequence, approximated linear models can be applied only in a limited range of plasma parameters. In general, the nonlinear coupling between FR and CM is important for the evaluation of polarimetry parameters.

Recent developments of the JET far-infrared interferometer-polarimeter diagnostic.

The far-infrared diagnostic provides essential internal measurements of the plasma density and magnetic field topology (q-profile via Faraday rotation angle) in real-time. The diagnostic capabilities have recently been extended in a number of key areas. Fast interferometer data, with 10 µs time resolution, and a new MATLAB code have allowed improved analysis of the evolution of density profiles during fast events such as vertical plasma displacements, edge localized mode, pellet fuelling, and disruptions. Using the polarimeter measurements in real-time, a new calibration procedure has been developed based on a propagation code using the Mueller matrix formalism. A further major upgrade of the system is presently underway: adding a second color laser to the vertical channels and implementing a new phase counter based on analog zero crossing and field-programmable gate array boards.

Albumin/gentamicin microspheres produced by supercritical assisted atomization: optimization of size, drug loading and release.

In this work, the supercritical assisted atomization (SAA) is proposed, for the first time, not only as a micronization technology but also as a thermal coagulation process for the production of bovine serum albumin (BSA) microspheres charged with Gentamicin sulfate (GS). Particularly, different water solutions of BSA/GS were processed by SAA to produce protein microspheres with different size and antibiotic content. SAA precipitation temperature was selected in the range 100-130 °C to generate protein coagulation and to recover micronized BSA in form of hydrophobic aggregates; GS loading was varied between 10% and 50% (w/w) with an encapsulation efficiency which often reached 100%. In all cases, spherical and noncoalescing particles were successfully produced with a mean particle size of 2 µm and with a standard deviation of about ±1 µm. The microspheres also showed a good stability and constant water content after 60 days of storage. The release profiles of the entrapped drug were monitored using Franz cells to evaluate the possible application of the produced microspheres in wound dressing formulations. Particularly, the microspheres with a BSA/GS ratio of 4:1 after the first burst effect (of 40% of GS loaded) were able to release the GS continuously over 10 days.

A new calibration code for the JET polarimeter.

An equivalent model of JET polarimeter is presented, which overcomes the drawbacks of previous versions of the fitting procedures used to provide calibrated results. First of all the signal processing electronics has been simulated, to confirm that it is still working within the original specifications. Then the effective optical path of both the vertical and lateral chords has been implemented to produce the calibration curves. The principle approach to the model has allowed obtaining a unique procedure which can be applied to any manual calibration and remains constant until the following one. The optical model of the chords is then applied to derive the plasma measurements. The results are in good agreement with the estimates of the most advanced full wave propagation code available and have been benchmarked with other diagnostics. The devised procedure has proved to work properly also for the most recent campaigns and high current experiments.

Physical characteristics and aerosol performance of naringin dry powders for pulmonary delivery prepared by spray-drying.

The aim of the present work was to develop dry powders containing naringin for a direct administration to the lung to combat oxidative stress. Naringin microparticles were prepared by spray-drying the neat flavonoid (2-5% w/v) from different water/ethanol co-solvents. The spray-dried powders were characterised for morphology, density, particle size distribution, residual humidity, crystallinity, solubility, thermal behaviour and respirable fraction. The fine fraction of the powders was measured by single-stage glass impinger and Andersen cascade impactor, using the Turbospin device for the deposition tests, wherein the dose to be aerosolised was premetered in a gelatine capsule. By increasing the ethanol content, the feed liquid turned from a suspension into a solution: the spray of flavonoid suspensions led to powders with high crystallinity degree, low water solubility and high bulk density, while the spray of drug solutions led to more amorphous particles, with higher solubility, lower density and improved aerodynamic behaviour. The optimisation of the operative parameters produced enhanced aerosol performance of the flavonoid powders containing only the active compound.

SNOM images of X-ray radiographs at nano-scale stored in a thin layer of lithium fluoride.

In this work, we report a method to observe soft X-ray radiographs at nanoscale of various kind of samples, biological and metallic, stored in a thin layer of lithium fluoride, employing scanning near-field optical microscopy with an optical resolution that reaches 50 nm. Lithium fluoride material works as a novel image detector for X-ray nano-radiographs, due to the fact that extreme ultraviolet radiation and soft X-rays efficiently produce stable point defects emitting optically stimulated visible luminescence in a thin surface layer. The bi-dimensional distribution of the so-created defects depends on the local nanostructure of the investigated sample.

Epidemiology and molecular analysis of herpes simplex keratitis requiring primary penetrating keratoplasty.

AIMS: To determine whether herpes simplex keratitis (HSK) has declined as an indication for penetrating keratoplasty (PKP) at the University of California San Francisco (UCSF) over the past 30 years. METHODS: Records of the Hogan Eye Pathology Laboratory were reviewed to determine the incidence of PKP performed for HSK from 1972 through 2001. Archived corneal tissue with the diagnosis of HSK was evaluated for herpes simplex virus (HSV) DNA by polymerase chain reaction (PCR) based assays. RESULTS: The number of corneal buttons submitted with the clinical diagnosis of HSK decreased from 1972 to 2001, while the overall number of PKPs performed did not. The percentage of corneal buttons with a clinical diagnosis of HSK that contained detectable HSV DNA did not change over the course of the study period. CONCLUSION: HSK declined as an indication for PKP from 1972 to 2001 at UCSF. It is unlikely that this decline was the result of improved diagnostic accuracy since detection of HSV DNA in corneal buttons with a clinical diagnosis of HSK was similar at the beginning and end of the study period.

Polymerase chain reaction based detection of fungi in infected corneas.

AIMS: To evaluate a polymerase chain reaction (PCR) based assay to detect fungi in scrapings from infected corneas. METHODS: A PCR assay was developed to amplify a portion of the fungal 18S ribosome gene. Corneal scrapings from 30 patients with presumed infectious keratitis were evaluated using this assay, as well as by standard microbiological techniques, and the results were compared. Conjunctival swabs from each patient's healthy, fellow eye were also evaluated by PCR. RESULTS: PCR and fungal culture results matched (were both positive or both negative for fungi) in 22 (74%) of 30 scrapings from infected corneas. Three (10%) of 30 samples were PCR positive but fungal culture negative; two of these appeared clinically to represent fungal infections, and the third was clinically indeterminate. Four (13%) scrapings were positive by PCR but also by bacterial and not fungal culture. One specimen (3%) was PCR negative but fungal culture positive. Of the conjunctival swabs from each patient's healthy fellow eye, five (17%) of 30 were positive by PCR, and the opposite, infected eye of all five of these harboured a fungal infection. CONCLUSIONS: PCR is promising as a means to diagnose fungal keratitis and offers some advantages over culture methods, including rapid analysis and the ability to analyse specimens far from where they are collected.

Utility of a polymerase chain reaction diagnostic system in a study of the epidemiology of shigellosis among dysentery patients, family contacts, and well controls living in a shigellosis-endemic area.

Polymerase chain reaction (PCR) diagnostic methods have rarely been used in epidemiologic studies of Shigella and enteroinvasive Escherichia coli (EIEC) infections. In this study, amplification of the invasion plasmid antigen H (ipaH) gene by PCR and standard culture methods was used to identify Shigella species or EIEC among 154 patients with dysentery, 154 age-matched controls, and family contacts in Thailand. The ipaH PCR system increased the detection of Shigella species and EIEC from 58% to 79% among patients with dysentery and from 6% to 22% among 527 family contacts; 75% of infections in family members were asymptomatic. Detection of the ipaH gene was statistically associated with dysentery. Household contacts of patients with shigellosis diagnosed only by PCR had significantly higher rates of shigellosis than household contacts of patients who did not have Shigella or EIEC infections. Detection of the ipaH gene by PCR is far more sensitive than detection by standard culture and is highly correlated with evidence of Shigella transmission among family contacts.