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Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Synthetic oligodeoxynucleotides containing bacterial CpG motifs trigger an immunomodulatory response that correlates with both the CpG hhhexamers and their flanking regions. In this study, four new phosphodiester backbone CpG ODNs were studied in the contest of the innate immune response to Mycobacterium tuberculosis (MTB) infection. Two out of the four CpG ODNs (CpG2 and CpG3) displayed significant and opposite immunomodulatory effects: CpG2 enhanced MTB containment by human Monocyte-Derived-Macrophages (MDM), while CpG3 promoted an increased pathogen growth, higher ROS and Labile Iron Pool (LIP) levels. Accordingly, for iron homeostasis genes transcription, CpG2 and CpG3 induced, respectively, an iron retention and iron release phenotype. Moreover, CpG2 induced NLRC4 and TRAF6 gene expression and repressed IKK alpha and TREM1 while CpG3 induced PPBP and IL-36 RN and repressed TRAF6, IL-1B, IL-1R2 and NF-kB2. After MTB infection, CpG2 increased the release of soluble TREM1 protein among many others as compared with fewer innate response-associated proteins induced by CpG3. We suggest that CpG2 helps the containment of MTB infection, by inducing an early tight balance of MDM activation players, including LIP, chemokines, ROS and TREM1 receptors. Oppositely, CpG3 induces in MDM an excessive and unregulated inflammatory response unable to contain MTB infection.

BACKGROUND Chronic cough is a common symptom, addressed in the clinical setting by empirical treatment together with some laboratory investigations. Purpose of the present study is to investigate the value of testing eosinophilic cationic protein (ECP) serum levels combined with other diagnostic procedures and empirical treatment in the diagnostic workup of chronic cough. METHODS In this study, we evaluated 194 patients with chronic cough. No subject had received any anti-inflammatory treatment before clinical evaluation, and none was an active smoker. ECP was measured with a commercially available fluoroenzyme immunoassay and results were expressed as µg/L. RESULTS The analysis of variance showed that mean ECP level differs among the various diagnosis categories (p < 0.001). Mean ECP level was significantly higher in asthmatic patients, particularly in the active disease. CONCLUSIONS Serum ECP concentration could represent a useful biomarker in the clinical work-up of chronic cough, managing to differentiate asthma from other chronic disorders.

A measure for portfolio risk management is proposed by extending the Markowitz mean-variance approach to include the left-hand tail effects of asset returns. Two risk dimensions are captured: asset covariance risk along risk in left-hand tail similarity and volatility. The key ingredient is an informative set on the left-hand tail distributions of asset returns obtained by an adaptive clustering procedure. This set allows a left tail similarity and left tail volatility to be defined, thereby providing a definition for the left-tail-covariance-like matrix. The convex combination of the two covariance matrices generates a “two-dimensional” risk that, when applied to portfolio selection, provides a measure of its systemic vulnerability due to the asset centrality. This is done by simply associating a suitable node-weighted network with the portfolio. Higher values of this risk indicate an asset allocation suffering from too much exposure to volatile assets whose return dynamics behave too similarly in left-hand tail distributions and/or co-movements, as well as being too connected to each other. Minimizing these combined risks reduces losses and increases profits, with a low variability in the profit and loss distribution. The portfolio selection compares favorably with some competing approaches. An empirical analysis is made using exchange traded fund prices over the period January 2006–February 2018.

Assuming a high education level associated with a high probability of job occupancy and greater income, comparative exercises analyzing academic performances and socioeconomic dynamics at regional, country, or supra-national scales have intensified in recent years. As far as tertiary education is concerned, a great disparity in academic performance was characteristic of OECD countries. While adults 25–34 years old were attaining tertiary degrees more frequently than adults 55–64 years old, adults 30–34 years old with at least one tertiary-educated parent were more likely to attain a tertiary degree than individuals from families whose parents have attended secondary—or at least primary—education. ‘Mobility’ and ‘opportunities’ are two dimensions of sustainable education systems that deserve further investigation when assessing disparities in academic performances as a possible source of unsustainable development and social polarizations. ‘Mobility’ refers to the probability of achieving tertiary education for children coming from families with a different—i.e., lower (e.g., secondary or primary)—level of education. ‘Opportunities’ refers to the probability for a child to attain tertiary education, regardless of the education level achieved by the parents. The present study proposes a quantitative assessment of both dimensions through an original approach and novel statistical measures ranking OECD countries. A comparison of individual rankings of ‘mobility’ and ‘opportunities’ reveals counterintuitive results in some cases. To overcome this issue, our study introduces aggregate methods combining the two measures with the aim of developing a bivariate ranking that accounts for both dimensions simultaneously and delineates a more complete evolution of academic performance divides in advanced economies.

Synthetic oligodeoxynucleotides containing bacterial CpG motifs trigger an immunomodulatory response that correlates with both the CpG hhhexamers and their flanking regions. In this study, four new phosphodiester backbone CpG ODNs were studied in the contest of the innate immune response to Mycobacterium tuberculosis (MTB) infection. Two out of the four CpG ODNs (CpG2 and CpG3) displayed significant and opposite immunomodulatory effects: CpG2 enhanced MTB containment by human Monocyte-Derived-Macrophages (MDM), while CpG3 promoted an increased pathogen growth, higher ROS and Labile Iron Pool (LIP) levels. Accordingly, for iron homeostasis genes transcription, CpG2 and CpG3 induced, respectively, an iron retention and iron release phenotype. Moreover, CpG2 induced NLRC4 and TRAF6 gene expression and repressed IKK alpha and TREM1 while CpG3 induced PPBP and IL-36 RN and repressed TRAF6, IL-1B, IL-1R2 and NF-kB2. After MTB infection, CpG2 increased the release of soluble TREM1 protein among many others as compared with fewer innate response-associated proteins induced by CpG3. We suggest that CpG2 helps the containment of MTB infection, by inducing an early tight balance of MDM activation players, including LIP, chemokines, ROS and TREM1 receptors. Oppositely, CpG3 induces in MDM an excessive and unregulated inflammatory response unable to contain MTB infection.

Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG4, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy).We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG4 specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patient.Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG4 showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM.In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

Pulmonary involvement in Sjogren syndrome (SS) could manifest as cystic lung disease (CLD). CLD in SS includes lymphocytic interstitial pneumonia (LIP) and pulmonary amyloidosis. Differential diagnosis usually requires surgical lung biopsy, whereas CT-guided percutaneous fine needle aspiration biopsy (CT-FNAB) has not yet explored. We describe the case of a 63-year-old never smoker Caucasian female with a SS diagnosis who displayed a newly detected diffuse CLD at high-resolution computed tomography, though totally asymptomatic. Given the favorable location of one big lesion at the superior left lobe, a CT-FNAB was proposed instead of a more invasive SLB. At histology examination a diagnosis of pulmonary nodular AL kappa amyloidosis in the context of SS was established. In conclusion, CT-FNAB might represent an alternative and less invasive diagnostic procedure than SLB in the differential diagnosis of CLD, even if further research is needed. Moreover, this case presents an unusual association between SS and pulmonary nodular AL kappa amyloidosis, with pulmonary nodules and cysts without systemic manifestations.

We develop an iterative procedure to generate stratification in non-overlapping classes of a population based on a one-dimensional variable, namely, the Italian income. The procedure works under the assumption that the income distribution is generated by a log-normal mixture of homogeneous income groups. The number of income groups is not determined a priori but rather endogenously by the iterative procedure that stops when the solution to a specific second-degree polynomial equation does not exist. We apply the approach to study the heterogeneity of Italian incomes and the poor population at regional level in the years 2005, 2010, and 2015. The cross-regional comparisons show differences in inequality and stratification dynamics while comparisons over time show the evolution of the classes.

Detecting the presence, the position and the extension of architectural coverings separations, both on horizontal and vertical layers – such as mosaics, plasters, slabs or other functional and decorative layers – is at the base of the analysis of the state of conservation of ancient structures. Non-destructive investigations used to find detachments, like Laser Doppler Vibrometry (LDV), are hardly executable in situ. They are also influenced by the boundary conditions and often need the intervention of onerous technical consultations. For this reason, traditionally, conservators rely on the technique of auscultation, which entails gently knocking with the hand, listening to the sound produced by the surface and perceiving the vibration of it. Together with the thermographic analysis, the results of these examinations are translated into the graphic documentation of the discontinuities of the structural elements, detachments and cracks between layers, in order to achieve the conservative diagnosis and outline a project of intervention. Analysis carried out with such method is accurate, but introduces a strong subjective conservator's connotation, which makes it not repeatable. In this contribution, after having briefly examined the state of the art of in situ technologies, an innovative acoustic-vibrational technique for the detection of detachment phenomena between layers and discontinuity is introduced. The proposed technique also allows tracing an accurate map, using an image correlation method between an acoustic “snap” of the point of interest and a “reference snap”. The analysis of the entire surface produces a graphics map of the detachments. This graphic documentation represents the “acoustic signature” of the structure, i.e. the “status quo” of the surface during the analysis. This representation can be used to monitor the state of conservation of the structure over time. In this paper, the method is developed and tested in laboratory using a personal computer and a hardware device specifically designed and fabricated, with the aim of providing a qualitative yet repeatable assessment of the state of conservation of a covering. The proposed method could be implemented in an easy-to-use and inexpensive portable version of the system using a smartphone, to which the developed hardware device would be connected through the audio jack to acquire the acoustic information, making the new system suitable for “in situ” operation. It can be also used for monitoring the evolution of the conservative scenario. The first results achieved on a test object are showed.

Assuming a high education level associated with a high probability of job occupancy and greater income, comparative exercises analyzing academic performances and socioeconomic dynamics at regional, country, or supra-national scales have intensified in recent years. As far as tertiary education is concerned, a great disparity in academic performance was characteristic of OECD countries. While adults 25–34 years old were attaining tertiary degrees more frequently than adults 55–64 years old, adults 30–34 years old with at least one tertiary-educated parent were more likely to attain a tertiary degree than individuals from families whose parents have attended secondary—or at least primary—education. ‘Mobility’ and ‘opportunities’ are two dimensions of sustainable education systems that deserve further investigation when assessing disparities in academic performances as a possible source of unsustainable development and social polarizations. ‘Mobility’ refers to the probability of achieving tertiary education for children coming from families with a different—i.e., lower (e.g., secondary or primary)—level of education. ‘Opportunities’ refers to the probability for a child to attain tertiary education, regardless of the education level achieved by the parents. The present study proposes a quantitative assessment of both dimensions through an original approach and novel statistical measures ranking OECD countries. A comparison of individual rankings of ‘mobility’ and ‘opportunities’ reveals counterintuitive results in some cases. To overcome this issue, our study introduces aggregate methods combining the two measures with the aim of developing a bivariate ranking that accounts for both dimensions simultaneously and delineates a more complete evolution of academic performance divides in advanced economies.

BACKGROUND AND OBJECTIVE: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients. However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF. METHODS: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer. KEY CONTENT AND FINDINGS: The data here presented mainly focus on gene mutations, epigenetics and novel therapeutic approaches. Moreover, epidemiology, prognostic variables and in new treatment strategies adopted in patients with IPF and lung cancer are discussed as well. CONCLUSIONS: Overall, the findings of this narrative review will be of help in defining the key molecular features that could applied in IPF setting with promising rationale to improve therapy and to better manage those cases carrying IPF and cancer concomitantly.

The technique of panel painting played a particularly significant role in Italian art, especially between the thirteenth and sixteenth centuries, before canvas came into general use. The conservation of panel paintings, however, is complex and largely depends on the original materials and techniques used to create the support and the many layers of preparation for painting. The state of conservation is influenced also by the history of stress/deformation that the painting has undergone and the microclimatic conditions in which it is exposed. The large thermo-hygrometric variation induces changes in the structure of the wood and can create cracks even for the gypsum which is more rigid than the wood and can develop dangerous detachments. Recently, a low-cost, portable test system for the measurement of detachments between layers of architectural coatings, called PICUS, inspired by the method used by restorers during diagnosis and conservation interventions, has been successfully developed. The same system was then tested to acquire information about the execution technique, the state of conservation and previous interventions of stratified structures such as paintings on wood.

We present A 60-year-old woman with a 2-year history of progressive anterograde memory deficit, with a A 18F-FDG PET/CT and 11C-PIB PET/CT studies performed. In the follow-up she presented a typical corticobasal syndrome with extrapyramidal signs and left superior limb dystonia. These clinical and imaging features are consistent with a focal presentation of AD.

We consider the problem of governing systemic risk in a banking system model. The banking system model consists in an initial value problem for a system of stochastic differential equations whose dependent variables are the log-monetary reserves of the banks as functions of time. The banking system model considered generalizes previous models studied in Fouque and Sun (in: Fouque and Langsam (eds) Handbook of systemic risk, Cambridge University Press, Cambridge, pp 444–452, 2013), Carmona et al. (Commun Math Sci 13(4):911–933, 2015), Garnier et al. (SIAM J Financ Math 4:151–184, 2013) and describes an homogeneous population of banks. Two distinct mechanisms are used to model the cooperation among banks and the cooperation between banks and monetary authority. These mechanisms are regulated respectively by the parameters $$\alpha $$ and $$\gamma $$ . A bank fails when its log-monetary reserves go below an assigned default level. We call systemic risk or systemic event in a bounded time interval the fact that in that time interval at least a given fraction of the banks fails. The probability of systemic risk in a bounded time interval is evaluated using statistical simulation. A method to govern the probability of systemic risk in a bounded time interval is presented. The goal of the governance is to keep the probability of systemic risk in a bounded time interval between two given thresholds. The governance is based on the choice of the log-monetary reserves of a kind of “ideal bank” as a function of time and on the solution of an optimal control problem for the mean field approximation of the banking system model. The solution of the optimal control problem determines the parameters $$\alpha $$ and $$\gamma $$ as functions of time, that is defines the rules of the borrowing and lending activity among banks and between banks and monetary authority. Some numerical examples are discussed. In particular during a two year period we consider the governance of systemic risk in the next year when governance decisions are taken quarterly. The systemic risk governance is tested in absence and in presence of positive and negative shocks acting on the banking system.

This paper formulates a portfolio optimization in a friction market as a suitable stochastic control problem with hyperbolic absolute risk aversion utility functions under a specific functional form of the amount of wealth invested in the risky asset inspired by the Merton optimal dynamics. The state variable is the amount of wealth invested in the risky asset, while the control variable is the share rate. This formulation has two advantages. First, it provides a portfolio where the optimality is obtained by minimizing the probability of large changes in the portfolio composition with consequently low frictions, while allowing for an explicit solution to the optimal control problem. Second, with this formulation, it can be proven that this optimal solution is the optimal solution of the frictionless Merton problem for corrected price dynamics. The corrected dynamics shows that the market friction increases the risk premium by an additional term that is an elementary function of the risk associated with the market frictions, as well the price of the risk, which also depends on the risk aversion of the investor. In addition, the corrected dynamics supports the existence of a shadow price in friction markets as already shown in Kallsen and Muhle-Karbe (2010). Finally, an empirical analysis to assess the model performance is illustrated on five-minute data of four major traded stocks, three market indexes, and four exchange rates including the Bitcoin/USD rate.