DNA Methylation in Nasal Epithelium: Strengths and Limitations of an Emergent Biomarker for Childhood Asthma.

Asthma is one of the most widespread chronic respiratory conditions. This disease primarily develops in childhood and is influenced by different factors, mainly genetics and environmental factors. DNA methylation is an epigenetic mechanism which may represent a bridge between these two factors, providing a tool to comprehend the interaction between genetics and environment. Most epidemiological studies in this field have been conducted using blood samples, although DNA methylation marks in blood may not be reliable for drawing exhaustive conclusions about DNA methylation in the airways. Because of the role of nasal epithelium in asthma and the tissue specificity of DNA methylation, studying the relationship between DNA methylation and childhood asthma might reveal crucial information about this widespread respiratory disease. The purpose of this review is to describe current findings in this field of research. We will present a viewpoint of selected studies, consider strengths and limitations, and propose future research in this area

A FAST MODEL FOR FLOW AND POLLUTANT DISPERSION AT THE NEIGHBOURHOOD SCALE

This paper deals with the development of a simple urban model for flow and dispersion in the urban canopy layer (UCL). The flow module of the model calculates spatially-averaged wind profiles adopting a technique recently proposed in the literature, which is based on a balance equation between the obstacle drag force and the local shear stress. Spatially-averaged wind profiles are used as input for a newly proposed dispersion model which solves the advection-diffusion equation at neighbourhood scale. In the model, the effects of the buildings within the UCL are taken into account by means of morphological parameters λf and λp (the ratios of plan area and frontal area of buildings to the lot area). Spatially-averaged mean concentrations output by the developed model are compared with numerical results obtained from the computational fluid dynamics (CFD) model FLUENT. In particular, two configurations of constant height UCL have been considered, which refer to as λp = λf = 0.16 and λp = λf = 0.44. The originality of the study is that the dispersion model itself integrates the equations without explicitly resolving the flow around individual buildings but still accounts for their effects. The computational costs are much reduced which makes it suitable for the predictions of concentrations over the neighbourhood scale in an operational context

Comparison Between Kidney Transplantation After Circulatory Death and After Brain Death: A Monocentric Retrospective Study After 1 Year of Follow-up

Background: Donation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. Methods: DCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation. We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with \u3c72 test for frequencies were elaborated. Results: Twenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 \ub1 25.3 and 54.71 \ub1 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). Conclusions: Controlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results

Prediction of severe thunderstorm events with ensemble deep learning and radar data

The problem of nowcasting extreme weather events can be addressed by applying either numerical methods for the solution of dynamic model equations or data-driven artificial intelligence algorithms. Within this latter framework, the most used techniques rely on video prediction deep learning methods which take in input time series of radar reflectivity images to predict the next future sequence of reflectivity images, from which the predicted rainfall quantities are extrapolated. Differently from the previous works, the present paper proposes a deep learning method, exploiting videos of radar reflectivity frames as input and lightning data to realize a warning machine able to sound timely alarms of possible severe thunderstorm events. The problem is recast in a classification one in which the extreme events to be predicted are characterized by a an high level of precipitation and lightning density. From a technical viewpoint, the computational core of this approach is an ensemble learning method based on the recently introduced value-weighted skill scores for both transforming the probabilistic outcomes of the neural network into binary predictions and assessing the forecasting performance. Such value-weighted skill scores are particularly suitable for binary predictions performed over time since they take into account the time evolution of events and predictions paying attention to the value of the prediction for the forecaster. The result of this study is a warning machine validated against weather radar data recorded in the Liguria region, in Italy

A FAST MODEL FOR FLOW AND POLLUTANT DISPERSION AT THE NEIGHBOURHOOD SCALE

This paper deals with the development of a simple urban model for flow and dispersion in the urban canopy layer (UCL). The flow module of the model calculates spatially-averaged wind profiles adopting a technique recently proposed in the literature, which is based on a balance equation between the obstacle drag force and the local shear stress. Spatially-averaged wind profiles are used as input for a newly proposed dispersion model which solves the advection-diffusion equation at neighbourhood scale. In the model, the effects of the buildings within the UCL are taken into account by means of morphological parameters λf and λp (the ratios of plan area and frontal area of buildings to the lot area). Spatially-averaged mean concentrations output by the developed model are compared with numerical results obtained from the computational fluid dynamics (CFD) model FLUENT. In particular, two configurations of constant height UCL have been considered, which refer to as λp = λf = 0.16 and λp = λf = 0.44. The originality of the study is that the dispersion model itself integrates the equations without explicitly resolving the flow around individual buildings but still accounts for their effects. The computational costs are much reduced which makes it suitable for the predictions of concentrations over the neighbourhood scale in an operational context

Variable echo time imaging for detecting the short T2* components of the sciatic nerve: a validation study

OBJECTIVE: The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve. MATERIALS AND METHODS: 15 healthy subjects (M/F: 9/6; age: 21-62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison. RESULTS: There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68-0.7; inter-rater 0.70-0.72) and the related aT2* measures (intra-inter reader ICC 0.95-0.97; 0.66-0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo. DISCUSSION: Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort

Oncological outcomes in fertility-sparing treatment in stage IA-G2 endometrial cancer

Background: The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins. Study design: Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were “endometrial cancer” AND “fertility sparing” AND “oncologic outcomes” AND “G2 or stage IA”. Results: A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months. Conclusions: Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased

Leftovers:The presence of manufacture-derived aquatic lipids in Alaskan Pottery

Lipids preserved within the walls of ancient pottery vessels are routinely analysed to reveal their original contents. The provenience of aquatic lipids in pottery is generally connected to vessel function (e.g., for cooking or storing fish, shellfish and aquatic mammals). However, ethnographic reports from early historic Alaska mention the use of aquatic oils for waterproofing low-fired pottery. Results of lipid residue studies on Alaskan pottery reflect an exclusive function of pottery to process aquatic resources. However, can one be sure these residues are the product of vessel function and not a remnant of the manufacturing process? The study presents the results of an experiment where the preservation of aquatic lipids during the firing process at different temperatures was measured. It was found that nearly all lipids were removed at firing temperatures of ≥ 400°C. Petrographic analysis of Alaskan pottery samples indicates that firing temperatures were generally &gt; 550°C but &lt; 800°C. The contribution of pre-firing manufacture-derived lipids to samples fired at these temperatures may be regarded as negligible. While the possible presence of aquatic lipids from post-firing surface treatments cannot be excluded, such treatments appear unnecessary for well-fired pottery.</p

TM5-FASST: a global atmospheric source–receptor model for rapid impact analysis of emission changes on air quality and short-lived climate pollutants

This paper describes, documents, and validates the TM5-FAst Scenario Screening Tool (TM5-FASST), a global reduced-form air quality source–receptor model that has been designed to compute ambient pollutant concentrations as well as a broad range of pollutant-related impacts on human health, agricultural crop production, and short-lived pollutant climate metrics, taking as input annual pollutant emission data aggregated at the national or regional level. The TM5-FASST tool, providing a trade-off between accuracy and applicability, is based on linearized emission-concentration sensitivities derived with the full chemistry-transport model TM5. The tool has been extensively applied in various recent critical studies. Although informal and fragmented validation has already been performed in various publications, this paper provides a comprehensive documentation of all components of the model and a validation against the full TM5 model. We find that the simplifications introduced in order to generate immediate results from emission scenarios do not compromise the validity of the output and as such TM5-FASST is proven to be a useful tool in science-policy analysis. Furthermore, it constitutes a suitable architecture for implementing the ensemble of source–receptor relations obtained in the frame of the HTAP modelling exercises, thus creating a link between the scientific community and policy-oriented users.</p