Seismic Delineation Of A Geothermal Reservoir

Surface seismic reflection surveys and VSP's have been extensively carried out in the Monteverdi area, within the Larderello region. Calibration of these seismic observations with data from numerous deep wells allowed the interpretation of the 2-D traverses so that a good geologic-structural reconstruction for the whole area was achieved. Many important reflectors were detected inside the Metamorphic basement by VSP's acquired in several wells in the area. These reflections were attributed to changes in petrophysical characteristics of the medium, particularly changes in fracture density, rather than to contrasts in lithology. Since at this time the main goal of the exploration in the Larderello region is the location of producing layers inside the basement, a major effort was applied to acquiring and modeling numerous VSP's in existing wells. In particular, a multioffset VSP was carried out in the COLLA 2 well with the specific goal of detecting fractured horizons within the reservoir of the Monte:verdi area. Because of the three-dimensionality of the seismic wave propagation in such a complicated geological structure, the standard onedimensional VSP modeling is not reliable. Therefore, 2-D and 3-D methods of modeling were applied. The modeling of the VSP data predicts important reflections at the depths corresponding to the main fractured zones intersected by drilling. These fractured zones should show subhorizontal distribution and thickness of tens of meters

ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by high heritability. It is known that genetic factors contribute to ASD pathogenesis. In particular, copy number variants (CNVs) are involved in ASD susceptibility and can affect gene expression regulation. 2p11.2 microdeletions encompassing ELMOD3, CAPG and SH2D6 genes have been described in four unrelated ASD families. The present study revealed that this microdeletion is responsible for the production of a chimeric transcript generated from the fusion between ELMOD3 and SH2D6. The identified transcript showed significantly higher expression levels in subjects carrying the deletion compared to control subjects, suggesting that it is not subjected to nonsense-mediated decay and might encode for a chimeric protein. In conclusion, this study suggests the possible involvement of this gene fusion, together with the other previously identified variants, in ASD

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience in the referral centre of Siena

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and has a median survival after diagnosis of 2–5 years. Pirfenidone is the first approved antifibrotic drug for the treatment of IPF. Here we report the functional progress, side effects and survival data of a population of patients with IPF, diagnosed at our centre and treated with pirfenidone. Methods: We enrolled 91 patients with IPF (71 males) treated with pirfenidone. Clinical, survival and functional details were collected retrospectively at start of therapy and after 12, 24, 36 and 48 months of treatment. Lung function tests at least 12 months before starting therapy were available for 40 patients and were entered in the database, as well as side effects. Results: During the observation period (922 ± 529 days), 27 patients died, 5 patients underwent lung transplant and 10 patients interrupted therapy due to adverse events or IPF progression. The median survival was 1606 days. There was a significant reduction in disease progression rate, as measured by trend of forced vital capacity, after 1 year of therapy with respect to before treatment (p = 0.0085). Forced vital capacity reduction rate was progressively higher in the subsequent years of treatment. Treatment-related side effects were reported in 25 patients and were predominantly mild. Overall, four patients discontinued therapy due to severe photosensitivity. Conclusions: Our findings confirm the efficacy of pirfenidone in reducing functional progression of IPF and its excellent safety profile in a real-life setting. This study, designed on a long-term follow up, contributes to the growing evidence on safety, tolerability and efficacy of pirfenidone in IPF. The reviews of this paper are available via the supplemental material section

Collagen Type IV Alpha 5 Chain in Bronchiolitis Obliterans Syndrome After Lung Transplant: The First Evidence

Introduction: Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometry pattern without parenchymal opacities. The protein signature of BOS lesions concerns extracellular matrix organization and aberrant basement membrane composition. In this pilot study, we investigated the presence of COL4A5 in the serum of patients with BOS. Methods: 41 patients who had undergone LTX were enrolled. Of these, 27 developed BOS and 14 (control group) were considered stable at the time of serum sampling. Of BOS patients, serum samples were analysed at the time of BOS diagnosis and before the clinical diagnosis (pre-BOS). COL4A5 levels were detected through the ELISA kit. Results: Serum concentrations of COL4A5 were higher in pre-BOS than in stable patients (40.5 ± 13.9 and 24.8 ± 11.4, respectively, p = 0.048). This protein is not influenced by comorbidities, such as acute rejection or infections, or by therapies. Survival analysis also reveals that a higher level of COL4A5 was also associated with less probability of survival. Our data showed a correlation between concentrations of COL4A5 and FEV1 at the time of diagnosis of BOS. Conclusion: Serum concentrations of COL4A5 can be considered a good prognostic marker due to their association with survival and correlation with functional parameters

An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 7 10-5 ). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders